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S136952742030031X
A primary goal of synthetic biology is to develop gene circuits that perform their intended functions despite variations in the growth conditions . However this has turned out to be more complicated than it originally seemed because there is a complex interplay between the operation of synthetic gene circuits and the g...
The lack of predictive understanding of circuit behavior limits synthetic biology. A major reason for this is the complex interplay between circuit and host state. Quantitative models promise to unravel this phenomenon and overcome this limitation.
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With more than one million bacterial genome sequences uploaded to public databases in the last 25 years genomics has become a powerful tool for studying bacterial biology . Here we review recent approaches that leverage large numbers of whole genome sequences to decipher the spread and pathogenesis of bacterial infecti...
72 of the available 1. None. 067. None. 277 bacterial genomes on NCBI are from only 10 species. WGS is a new gold standard for detection of clonal outbreaks and transmission events. WGS ancestral reconstruction and GWAS allow unbiased functional prediction. WGS of longitudinal infection can be used to detect host adapt...
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is known for its intrinsic resistance to conventional antibiotic treatment and hypervirulence during infection . This coupled with its extraordinary capacity to survive in myriad harsh environments has led to increasing rates of infection in clinical settings . Numerous studies have characterized the virulence factors ...
encodes a variety of transcription factors two component systems and small RNAs that influence survival during infection. ABUW 1645 is a novel regulator that serves as a switch between avirulent and virulent phenotypes during infection within the host. The two component system BfmRS regulates pathways involved in cell ...
S1369527420300370
Invasive fungal infections are responsible for a significant disease burden worldwide . Drugs to treat these infections are limited to only four unique classes and despite these available treatments mortality rates remain unacceptably high . In this review we will discuss antifungal drug screening and how the approach ...
There is an urgent need for the development of novel antifungals. Repeating the same growth assays leads to reidentification of the same molecules. Designing creative screening strategies will diversify leads identified for antifungal development.
S1369527420300394
Introduction of antibiotics into clinical use has contributed to some of the greatest improvements to public health in the 20th century . Most antibiotics are based on antimicrobials that were isolated from environmental microorganisms over 50 years ago but emerging resistance requires discovery of new molecules and de...
Most antibiotics are derived from antimicrobials produced by soil microorganisms. Genetic potential of microbes far exceeds their small molecule output in the lab. Microbial ecology informs strategies to discover new antimicrobials. Organisms from non conventional habitats may serve as a source of new antimicrobials. B...
S1369527420300400
is both a member of the human mucosal microbiota and a common agent of invasive fungal disease . Systems biology approaches allow for analysis of the interactions between this fungus and its mammalian host . Framing these studies by considering how
Interactions between. and human hosts shape each others biology. Systems biology provides tools to interrogate these interactions at multiple scales. Microscopy transcriptomics and proteomics illustrate individual cell responses. Functional genomics screens and experimental evolution reveal genotypes that impact fitnes...
S1369527420300412
Many bacterial pathogens rely on dedicated secretion systems to translocate virulence proteins termed effectors into host cells . These effectors engage and manipulate host cellular functions to support bacterial colonization and propagation . The secretion systems are molecular machines that recognize targeting featur...
Effector arsenal expansion may facilitate bacterial infection of a broader range of hosts. Computational machine learning has facilitated large scale effector discovery. Substantiating the biological significance of. identified effectors remains challenging.
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Anti fungal immunity is characterized by the continuous interplay between immune activation and immune regulation processes . These processes have now been clearly shown not only in animal pre clinical models but also in humans . To create and maintain this immune homeostasis reciprocal interactions among the host immu...
The increased incidence of human fungal infections is related to immune disorders. Humans are holobionts maintaining balanced interactions with pathobionts and the microbiome. The host microbiome contributes to both antifungal resistance and tolerogenic strategies. Organoids may be used as mini holobionts systems to mo...
S1369527420300631
Compared to bacteria fungi often exhibit a lower abundance and a higher temporal volatility in the intestinal microbiota . Analysis of fungi in the microbiota faces technical limitations with tools that were originally developed for analyzing bacteria . Dysbiotic states of the intestinal mycobiota often associated with...
The human mycobiota contains clinically relevant fungal species. Longitudinal sampling provides robust insights into the human mycobiota. Simultaneous analysis of intestinal fungi and bacteria is critical in clinical studies. The intestinal mycobiota is an important source of fungal bloodstream infections. The mycobiot...
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is a major cause of fungal nosocomial infections . Host defense against disseminated infections caused by this yeast strongly relies on myeloid cells of the innate immune system . Recently several breakthroughs have been made that significantly improved our understanding of the role of macrophages during candidiasis an...
Tissue resident macrophages are central to counteract systemic candidiasis. Macrophages engulf yeast but struggle with hypha forming frustrated phagosomes. evolved strategies to counteract the microbicidal phagosomal environment. can employ four distinct mechanisms to escape from macrophages. Modulation of macrophage a...
S1369527420300655
Although soluble mediators of our innate immune system have a substantial impact on invading microbes their role against fungal pathogens has been underexplored . Constituting the humoral immunity soluble mediators comprise the complement system collectins acute phase proteins antibodies and antimicrobial peptides . Th...
Soluble mediators exert antifungal properties directly or indirectly. They are unaffected or partially affected by immunosuppression unlike cellular immunity. Most soluble mediators are pattern recognition receptors linking fungi to phagocytes. Soluble mediator based antifungal immunotherapies are gaining attention. Im...
S1369527420300679
Impaired microbiome diversity and composition can develop into a potent etiological agent of disease and increase susceptibility to infection . Given this interventions targeting the microbiome have developed rapidly with healthy donor feces being a
Fecal transplants despite associated risks are now a widely accepted therapeutic. Bacterial species and functions consistently associated with efficacy have been identified. Recent research indicates fungi and viruses are associated with therapy outcomes. Limited data exists on the influence of host diet and genetics o...
S1369527420300680
Bacterial pathogens need to sense and respond to their environments during infection to align cell metabolism and virulence factor production to survive and battle host defenses . Complex regulatory networks including ligand binding transcription factors two component systems RNA binding proteins and small non coding r...
Regulators act as genetic time circuits to adjust metabolism and virulence. Altered metabolic flux has profound effects on survival and pathogenic potential. Host signals or nutrients can affect gene expression on various spatial scales. Spatial and temporal cues result in metabolic and phenotypic heterogeneity.
S1369527420300692
Directed evolution allows the effective engineering of proteins biosynthetic pathways and cellular functions . Traditional plasmid based methods generally subject one or occasionally multiple genes of interest to mutagenesis require time consuming manual interventions and the genes that are subjected to mutagenesis are...
Methods for targeted microbial mutagenesis enable the massively parallel engineering of proteins biosynthetic pathways and cellular functions. ssDNA based recombineering and CRISPR Cas9 genome editing allow for precise saturation mutagenesis at user defined genomic sequences. Recombineering allows the most extensive an...
S1369527420300709
Early life is a critical time window for the neonatal gut to be progressively populated with different bacterial species that collectively promote gut maturation . A fully developed and healthy gut microbiome in neonates is an important driver for the development of other aspects of health . Unlike the relatively stabl...
microbial stimulation modulates both prenatal and postnatal immune cell development. Unique neonatal gut microenvironment allows for progressive colonization of selective bacteria before stabilization of the gut microbiome. Both mode of delivery and nutritional availability heavily shape postnatal colonization of gut b...
S1369527420300710
Antibiotics used in combination are an effective strategy for combatting numerous infectious diseases in clinical and veterinary settings particularly as a last line therapy for difficult to treat cases . Combination therapy can either increase or slow the rate of killing broaden the antibiotic spectrum reduce dosage a...
Combination therapy is an important tool for tackling antibiotic resistance. In depth molecular studies for combination therapy are lacking. We summarise six major mechanisms mediating the effects seen in synergy and antagony. Combination therapy resistance mechanisms are complex on a population level. Resistance mutat...
S1369527420300734
Phage satellites are genetic elements that depend on helper phages for induction packaging and transfer . To promote their lifestyles they have evolved elegant and sophisticated strategies to inhibit phage reproduction which will be reviewed here . We will principally focus on the convergent interference mechanisms use...
Phage satellites have evolved multiple and convergent strategies to inhibit phage reproduction. Production of small phage capsids is a universal mechanism used by satellite phages to inhibit phage maturation. Satellite phages have evolved mechanisms that promote their own packaging and transfer.
S1369527420300746
Once overlooked as passive bystanders of the human intestinal microbiota new evidence is shedding light on the importance of enterococci and their bacteriophages in shaping human health . Natural predators of enterococci phages represent a narrow spectrum precision targeting modality for the eradication of problematic ...
Phage bacteria interactions drive key fitness tradeoffs in enterococci. Discovery of novel phage receptors will aid in the future therapeutic development of enterococcal phages. Enterococcal phage therapy demonstrates efficacy in animal models yet studies in humans are currently lacking. Enterococcal gut dysbiosis exac...
S1369527420300758
To this day malaria remains a global burden affecting millions of people especially those in sub Saharan Africa and Asia . The rise of drug resistance to current antimalarial treatments including artemisinin based combination therapies has made discovering new small molecule compounds with novel modes of action an urge...
evolution and whole genome sequencing elucidates genedrug interactions. Cellular thermal shift assay and mass spectrometry directly reveals small molecule compoundprotein interactions. Metabolomic profiling complements target identification with broad mode of action.
S136952742030076X
Transfer RNAs are non coding RNAs essential for protein synthesis . tRNAs are heavily decorated with a variety of post transcriptional modifications . Recent methodological advances provide new tools for rapid profiling of tRNA modifications and have led to discoveries of novel modifications and their regulation . Here...
Diverse chemical modifications of tRNAs tRNA modifications modulate protein synthesis. tRNA sequencing and RNA mass spectrometry enable rapid identification of the structures and sites of tRNA modifications.. Novel modifications have been discovered in a variety of organisms. tRNA modification frequencies are regulated...
S1369527420300771
The lung is a central organ for immune environmental interactions ranging from tolerance against harmless substances to protection against pathogens which are particularly sensitive to regulation by the intestinal microbiota . Airborne fungi can cause variety of diseases including allergies and inflammatory disorders a...
Ubiquitous airborne fungi differentially induce protective immunity or tolerance. Chronic exposure to. induces primarily Treg mediated tolerance. The majority of. associated diseases resemble immune pathologies. Microbiota exert antigen specific and non specific innate immune modulation.
S1369527420300801
The complex communities of microbes that constitute the human microbiome are influenced by host and environmental factors . Here we address how a fundamental aspect of human biology blood type contributes to shaping this microscopic ecosystem . Although this question remains largely unexplored we glean insights from de...
A historical perspective on associations between ABO blood type and bacteria. Mechanisms that drive relationships between host blood type and commensal and pathogenic bacteria. Review of conflicting evidence for an influence of host blood type on the intestinal microbiome. How this knowledge may inform the development ...
S1369527420300813
Antimicrobial resistance is an urgent public health threat and continues to be on the rise . Basic microbiological research is the foundation for addressing knowledge gaps both for the development of new antibiotics diagnostics and preventives but also to inform strategies to mitigate the transmission of resistance and...
Antimicrobial resistance is on the rise globally. The pipeline for new antibiotics is weak due to market failure. New initiatives have been put in place to replenish the antibiotic R D pipeline. The Global Antimicrobial Research and Development Hub was founded to coordinate the R D space.
S1369527420300849
Myxobacteria conduct complex social traits that requires populations to be highly related and devoid of exploiters . To enrich for clonal cells in populations they employ kin discrimination mechanisms . One key system involves a polymorphic cell surface receptor TraA which recognizes self by homotypic interactions with...
Self recognition mediated by homotypic binding of a dynamic polymorphic cell surface receptor. TraA and TraB function as a fusogen that mediates outer membrane cargo exchange and homeostasis in. Polymorphic toxin exchange function as self identity barcodes. Experimental complexities in distinguishing greenbeard recogni...
S1369527420300904
Recent advances in genomics have uncovered the tremendous diversity and richness of microbial ecosystems . New functional genomics methods are now needed to probe gene function in high throughput and provide mechanistic insights . Here we review how the CRISPR toolbox can be used to inactivate repress or overexpress ge...
CRISPR screens enable the investigation of gene function in high throughput. CRISPR screens can be performed on bacteria or host cells. Cas9 and dCas9 are used to mutate genes or inhibit their expression respectively. Pooled and arrayed screens can access different phenotypes. New CRISPR technologies such as base editi...
S1369527420300928
As the incidence rate of invasive fungal infections has increased with the use of modern medical interventions so too has the occurrence of fungi invading the brain . Fungi such as
Brain fungal infections are a growing problem affecting both immunocompromised and putatively immunocompetent individuals. Fungi enter the brain by crossing the bloodbrain barrier or by direct inoculation. Resident and recruited immune cells are required to clear or contain brain fungal infection. Immune response often...
S1369527420300977
Antibiotics profoundly reduced worldwide mortality . However the emergence of resistance to the growth inhibiting effects of these drugs occurred . New approaches to treat infectious disease that reduce the likelihood for resistance are needed . In bacterial pathogens complex signaling networks regulate virulence . Ant...
Anti virulence therapies target intercellular signaling networks essential for acute infection. Quorum sensing QS mediates the transition from human commensal to opportunistic pathogen. Microbiota interference of pathogen signaling can be exploited to inhibit virulence. In chronic disease host selective pressures may m...
S1369527420300989
Clonal cell populations often display significant cell to cell phenotypic heterogeneity even when maintained under constant external conditions . This variability can result from the inherently stochastic nature of transcription and translation processes which leads to varying numbers of transcripts and proteins per ce...
Phenotypic heterogeneity is an inevitable consequence of gene expression. Gene expression noise has functional consequences e.g. survival differentiation . Emerging tools offer the potential to quantify and control noise in single cells.
S1369527420300990
The trillions of microbes that constitutively colonize the intestine impact diverse aspects of human physiology in health and disease . Immunoglobulin A is the most abundant antibody isotype produced at mucosal surfaces and nearly two grams of IgA is secreted into the intestine every day . Secretory IgA provides critic...
Secretory immunoglobulin A SIgA is the dominant antibody at mucosal surfaces. Gut commensals are coated by SIgA at varied levels. SIgA targeting regulates bacterial activities and shapes gut microbiota composition. SIgA enforces host microbiota homeostasis throughout the lifespan.
S1369527420301004
The mammalian immune system can tune its inflammatory response to the threat level posed by an invading pathogen . It is well established that the host utilizes numerous patterns of pathogenicity such as microbial growth invasion and viability to achieve this tuning during bacterial infections . This review discusses h...
Host fungal interactions tune the innate inflammatory response to maintain host resistance against distinct fungal isolates. Growth viability phagosome escape and cell wall changes are critical patterns of pathogenesis during fungal infection. Environmental evolution and growth conditions drive isolate specific virulen...
S1369527420301016
Environmental triggers in the context of genetic susceptibility drive phenotypes of complex immune disorders such as Inflammatory bowel disease . One such trigger of IBD is perturbations in enteric commensal bacteria fungi or viruses that shape both immune and neuronal state . The epigenome acts as an interface between...
Epigenetics is a therapeutically tractable mechanism linking genetics and environmental cues in IBD. Variants of human epigenetic regulators or regulatory regions associate with IBD susceptibility. Individual epigenetic enzymes exacerbate or protect mouse models of colitis. Intestinal bacteria modulate DNA histone modi...
S1369527420301028
Malaria continues to pose a severe threat to over half of the worlds population each year . With no long term effective vaccine available and a growing resistance to antimalarials there is a need for innovative methods of
Gut microbiota is associated with malaria in rodents and humans. Gut microbiota influences systemic adaptive immune responses. Probiotic treatment in infants can decrease infection related mortality.
S1369527420301053
A myriad of microbes living together with the host constitute microbiota which possesses very diverse functions in regulation of host physiology . Recently it has been unequivocally demonstrated that microbiota regulates cancer initiation progression and responses to therapy . Here we review known pro tumorigenic and a...
Microbiota is important in various aspects of host physiology including regulation of cancer development and progression. Microbiota can play negative or positive effects on tumorigenesis and efficacy of therapies. Microbiota regulates tumorigenesis via few distinct mechanisms including interactions with cancer cells a...
S1369527420301065
Human fungal diseases are a significant global health problem affecting both immunocompromised and immunocompetent patients . Although patients with single gene inborn errors account for only a small part of patients developing fungal infections studies of these diseases significantly promoted our understanding of the ...
Monogenetic causes of fungal disease promoted studies of antifungal immunity. Advances have been achieved in both novel genes and novel phenotypes. Defects in either innate or adaptive immune response underlie fungal susceptibility. Genetic causes should be considered in immunocompetent patients of unusual mycosis.
S1369703X19301354
Two lab scale sequencing batch biofilm reactors with no salt and 10.0g L salt were operated to explore the simultaneous COD nitrogen phosphorus removal behavior and the microbial diversity as well as tridimensional key functional microbial groups responses to varying C N P ratios from 125 8.3 1 to 33.3 8.3 1 . The simu...
Simultaneous nutrients removal in SBBRs were evaluated at varying C N P ratios. Lower C N P inhibited S SBBR more severely in terms of TP removal. Both the microbial diversity and richness were effected by C N P ratios. Microorganism in suspended sludge and biofilm showed different characteristics. PAOs and DNPAOs enri...
S1369703X19302694
Limiting nitrogen and excess carbon sources induce accumulation of the bioplastic Poly as inclusion bodies in microbes . Here we designed a co culture
Poly 3 hydroxybutyrate synthesis was increased using co culture strategy. Aeration and agitation optimization studies showed improved kLa. Metabolic heat released and yield coefficients were calculated. Synergy seen in co culture gave higher PHB yield compared to monocultures.
S1369703X19303304
The dissolved carbon dioxide effect on succinic acid production by A. succinogenes has been investigated and a double substrate mechanistic model has been developed to describe the bioconversion of glycerol under CO
We develop a new experimentally validated double substrate succinic acid fermentation model. The model accounts for multi phase mass transfer phenomena in the fermentation medium. Mass transfer effects of solid MgCO3 on the fermentation system are quantified. System dynamics including liquid and gaseous substrates are ...
S1369703X19303316
Shaken microwell plates are widely used for early bioprocess development as they allow a large number of experiments to be performed in parallel by using small amount of materials . Despite their widespread use microwell plates have not been characterised from an engineering viewpoint . In this study mixing time measur...
Reduced free surface oscillation leads to reduced mixing time in square microwell geometry. Surface tension plays a critical role in the mixing process in square microwell plates. Mixing times are longer in cylinder wells at low shaken speeds when compared to square microwells. Natural frequency is a promising scaling ...
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sp . has been reported to synthesize polyhydroxyalkanoates with different monomers such as 3 hydroxybutyrate and 3 hydroxyvalerate . In this study the PHA synthase gene of
Heterologous expression of. Kad1. gene into. PHB4. Transformant. Cn Kad1 harboring. produces P 3HB. 4HB . 4HB monomer increased with higher concentration of sodium 4HB as the carbon source. Produced copolymer with higher 4HB significantly reduced the melting temperature.
S1369703X19303353
Microalgal biorefineries have recently emerged as a potentially economically viable option for the co production of value added products and fuels such as biodiesel and biobutanol . Whilst microalgal biodiesel has been studied extensively microalgal biobutanol has received less attention due to the low product yields o...
We present a biorefinery approach for dual biofuel production from microalgae. Biobutanol production was achieved with both raw and hydrolysed biomass. Biodiesel extraction was enhanced by increased cell disruption treatments. ABE process was optimized by supplementing butyric acid to the fermentation medium.
S1369703X19303365
Fumaric acid is an industrially important platform chemical which has been widely used in food chemicals agriculture and pharmaceutical industries . Due to the rising price of raw materials in traditional petrochemical method and demand for sustainable development fermentative fumaric acid production has attracted grea...
This review provides an overview of metabolic pathways for fumaric acid production. Different fumaric acid producers and strain improvement strategies involved were introduced. Alternative substrates for fumaric acid production and their fermentation performances were shown. The optimization of fermentation conditions ...
S1369703X19303377
Robust microalgae cultivation at industrial scale needs complex scale up of photobioreactors since the same yields obtained at lab scale are hardly reached during pilot or industrial production . In this paper we propose a procedure based on Buckingham theorem to perform the scale up of photobioreactors used to cultiva...
Theoretical scale up of photobioreactors by Buckingham theorem. Dimensionless numbers evaluated by experimental campaign at different scales. Airlift reactors for cultivation of Chlorella Vulgaris at pilot scale. Set up and tuning of operating conditions for integration in biorefineries.
S1369703X19303389
Calcitonin gene related peptide promotes proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells which influence bone regeneration and reconstruction . We previously established CGRP modified BMSCs that express the CGRP gene and demonstrated that this elevated CGRP expression promotes osteoge...
CGRP could promotes the proliferation and osteogenic differentiation of BMSCs. CGRP modified BMSCs may promote bone formation and repair in the femoral head. CGRP modified BMSCs combined with autogenous bone grafting improved the success of treatment for ONFH.
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In this study the combined effect of dissolved oxygen and COD N on nitrogen removal as well as the corresponding mechanisms were investigated in aerated constructed wetlands . At each investigated COD N level the ammonium removal efficiency increased as DO concentration increased . However the highest total N removal e...
DO and COD N had a combined effect on nitrogen removal pathway in aerated CWs. SND was dominant N removal routine in a broad range of DO and COD N condition. SNAD was dominant N removal pathway at low DO along with low COD N levels. Optimal DO for TN removal should be adjusted according to influent COD N.
S1369703X19303419
Manganese peroxidase which is an extracellular glycosylated heme protein produced by various basidiomycetous fungi shows attractive potential in various biotechnological applications . A novel MnP gene
A novel MnP gene. from. BBP6 was cloned. Gene. was functionally expressed in. rMnP3 BBP6 had great potential in dye decolorization and denim bleaching. The first report on denim bleaching and PAH degradation using a recombinant WRF MnP.
S1369703X19303420
Eco friendly cost efficient and effective extraction methods have become significant for the industries applying zero waste principles . The two main objectives of this study were to examine fucoxanthin extraction from wet
SFE was performed to extract fucoxanthin from. Extraction was conducted directly from wet microalga to reduce energy and cost. A solvent to solid ratio of 200 1 20MPa 35C at 120rpm 60min yielded 0.69mg g. Residual biomass was characterized using light microscopy and SEM EDS analysis. Residual cells could be potential c...
S1369703X19303432
This research aimed at comparing the single stage and two stage co digestion of end of life dairy products with a mixture of agro industrial wastes . The two systems were operated in parallel and operational parameters including hydraulic retention time and organic loading rate were tested for their effect on bio hydro...
End of life dairy products EoL DP can be efficiently co digested with agro waste. The two stage system yielded 30 higher energy productivity than the single stage. EoL DP fermentation in 3 days HRT resulted in lactate accumulation and process failure. The co digestion systems were stable despite the high ammonia concen...
S1369703X19303511
Porous cellulose beads are widely used in the adsorption field in which enhancing the structure stability and enlarging the specific surface area are the ways to improve the adsorption efficiency . Here a preliminary chemical cross linking strategy is explored to construct the tough and highly porous cellulose beads as...
Porous cellulose beads were prepared by preliminary chemical cross linking strategy. The inner chemical linkages of neighboring cellulose chains strengthened the mechanical strength of cellulose beads. Porous cellulose beads possessed high specific surface area of 142.96m. The adsorption capacity of adsorbents reached ...
S1369703X19303560
When feeding enzymes are consumed by livestock and poultry the stomach is the first organ to come in contact with feeding enzymes . They will face major hazards acidolysis and enzymatic hydrolysis . Therefore it is very important to improve the tolerance of feed enzymes to the gastric juice such as pepsin . However the...
Inhibition of the transition state formation can improve the pepsin resistance of cellusase E4. Select proper mutable sites based on the hydrolysis preference of pepsin and rational design. The pepsin resistance of mutants were improved without affecting the enzymology. The universality of methods are fit to improve th...
S1369703X19303572
Online measurements of off gas streams are often crucial for studying bioconversion processes . However for anaerobic processes options for online off gas analysis are typically restricted to lab scale bioreactors or larger systems while gas measurements at smaller scales typically do not discriminate between different...
System developed to analyze headspace gasses in anaerobic shake flask fermentations. Fermentations in system mirrored those previously reported in stirred tank reactors. Analyses of gaseous and soluble products allowed carbon balances to be performed. Gas transfer rates reflected phenomena such as inhibition and substr...
S1369703X19303584
The wider application of creatinase an enzyme used to determine renal function is limited by the yield problem and current production can not meet the needs of society . Therefore the work constructed an efficient
Creatinase activity in B. subtilis was up to 141.9 U mL by high density fermentation. Calcein AM PI assays confirmed the cell membrane was damaged. TEM and SEM results found the presence of leakage site on the bacterial cell surface.
S1369703X19303596
An optimization workflow is introduced which integrates multi objective optimization of lignocellulolytic enzyme cocktail ingredients with a bioethanol production process where the enzymes are utilized . The workflow integrates data collection via exploratory experiments modeling via Kriging Pareto based multi objectiv...
growth conditions are optimized for Lac Bet and Cmc activities. A novel workflow integrating experiments and process simulations is offered. Kriging is used to model time profile data from activity measurements. The workflow is demonstrated on a bioethanol production process case study. Significance of Bet activity fav...
S1369703X19303602
A valuable monomer in the synthesis of various polyesters is 5 hydroxymethyl 2 furan carboxylic acid . In this work the synthesis of HMFCA using crude HMF obtained from fructose is described . To obtain crude HMF fructose dehydration was performed by thermal treatment with Nb
Crude HMF was transformed to HMFCA by. The HMFCA concentration of 790.2mg L was obtained using the fed batch strategy. Pyridine nucleotide disulfide oxidoreductase gene is related with HMFCA production.
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This work aims to investigate optimization while running a Recycled Membrane Biofilm Reactor as a sustainable biological treatment for microcystins removal . For this purpose coupons from an end of life seawater reverse osmosis membrane module were extracted and conditioned . The MC degrading biofilm formation on this ...
Biomass thickness and homogeneity of the biofilm were enhanced by air supply. A stable biofilm with EPS production was achieved on the recycled membrane. The air supply diminished the lag phase and increased the MC removal by the biofilm. MC was more rapidly eliminated in nutrient rich water.
S1369703X19303626
Using laccase as a case study an alternative methodology for discrimination of bisubstrate mechanism types useful for Bi Bi reactions when water is one of the products is presented . A purified enzyme from fungal cultures of
AICc and Akaike weights were useful to discriminate bisubstrate models of laccase reactions. The more likely bisubstrate model for ABTS oxidation was ping pong. The more likely bisubstrate model for DMP oxidation was Theorell Chance. Michaelis Menten constants towards dioxygen mean that laccase is not oxygen saturated.
S1369703X19303638
During the past two decades cell culture has played an important role in many biochemical and biomedical fields . However finding an alternative to animal serum is an important area in cell culture methods and related biotechnology industries . In a previous study we demonstrated that the platelet rich plasma from spec...
This study was the first to demonstrate that ectoine is an effective PRP activator. Ectoine is a novel activator with a defined and simple structure. Ectoine activated PRP can release high levels of bioactive molecules. Ectoine activated PRP is an excellent replacement for animal serum in cell ulture. Ectoine activated...
S1369703X1930364X
The expanding aquaculture industry increases the prices of fishmeal the main protein source in fish diet . A promising alternative is microalgal protein . Therefore we investigated the protein production capacities of green microalgae
Microalgal strains were optimized for protein production as alternative to fishmeal. After optimization the maximum cultivation time of both strains was 2 days. Maximum protein productivity for. CY1 was 0.8560.025g L d. Maximum protein productivity for. ESP 31 was 0.9460.065g L d.
S1369703X19303651
As a biocompatible and designer solvents ionic liquids are extensively used for enzymatic conversion of substrates particularly those that are insoluble or sparingly soluble in water and common organic solvents . More than a decade ago the first generation ILs involved in enzymatic reactions generally comprised an imid...
Overview of second and third generation ionic liquids ILs for enzymes. ILs showed great enhancement of enzyme performance. Novel materials have been developed to stabilize enzymes in ILs. More studies are required to develop cost analysis for ILs bioprocesse
S1369703X19303699
Lipid degradation behavior was examined during the Intermittent Contact Oxidation Process for application in in sewer purification . Lipids are known to accumulate in the sewer environment making the study of its degradation behavior relevant for in sewer purification . Changes in the lipid substrate during various flo...
Lipid degradation occurred during no flow and was enhanced during frequent flow. Oxygen mass transfer was enhanced during flow. Oxygen mass transfer during no flow was affected by retained water volume in the porous media. Oxygen supply affected by flow intermittency affected lipid degradation behavior.
S1369703X19303705
A new dynamic model that mimics gastrointestinal function was designed . Elastic and contractile silica gel with gastrointestinal rugae and folds were used to simulate the stomach and large intestine and silica gel with intestinal folds and villi was utilized to simulate small intestines . Mixing times for Newtonian fl...
BGR has better mixing time than traditional STR. The gastric pressure of the stomach can be simulated by adopting different motion models. The maximum crushing force of the BRG is higher than 0.72N. The folds and villi increased the surface area of small and large intestine walls by 112 and 52 . New technology for dyna...
S1369703X19303717
Indole 3 ethanol is an important pharmaceutical intermediate that possess significant pharmaceutical properties . In this study we established an artificial pathway in engineered
Production of indole 3 ethanol from L tryptophan. De novo biosynthesis of indole 3 ethanol from glucose. De novo biosynthesis of indole 3 ethanol acetate from glucose.
S1369703X19303729
As a kind of pyrimidine nucleoside cytidine has been widely recognized as an important precursor for the production of some antiviral and antitumor drugs . In this study the systematic construction of metabolically engineered
Cytidine titer was stepwise increased under the coordination of four modularized metabolic engineering strategies. The metabolic module from UMP toward cytidine was investigated to enhance cytidine formation. The major rate limiting steps and competing pathways of cytidine biosynthesis were identified and fine tuned. A...
S1369703X19303730
The aim of this study was to establish a phenomenological model capable of describing the mass transfer and kinetic effects of the
Phenomenological model for the. transesterification of microalgal biomass. The model predicts the mass transfer of the transesterification reaction. The model fits the experimental data and adequately describes the reaction kinetics. The Volume Elements Method was used in the model development
S1369703X19303754
Small scale culture of animal cells in suspension is of importance for many applications . At a small scale fed batch is achieved either by manual bolus feeding or the use of liquid handling robots . In this study we report an alternate application of a hydrogel for in situ continuous delivery of a nutrient feed compri...
In situ delivery of a multi component nutrient feed by hydrogel NutriGel . NutriGel sustains release of amino acids for at least 7 days. Independent modulation of release rates of 16 amino acids demonstrated. NutriGel enables a completely closed system for fed batch culture of animal cells. NutriGel improved IVCD and p...
S1369703X19303766
Understanding and modeling of the metabolic pathway of a cell by probing the fraction of extracellular metabolites is gaining much interest in biological reactions . This communication deals with metabolic footprinting technique to understand the effect of static and shake culture conditions on the production of lovast...
Metabolic pathway for the biosynthesis of lovastatin was constructed using metabolic footprinting technique. Culture conditions had profound influence on the production of lovastatin as observed through the variation in internal metabolic fluxes. Ethanol and glycerol were produced along with lovastatin by. They were pr...
S1369703X19303778
Realization of binding reagents that can perform high fidelity sequential recognition and detection of amino acids is important for the success of many proposed approaches for single molecule protein sequencing . Towards this purpose a variant of the
Engineering thermostable into ClpS protein variants for biotechnology applications. Thermostable ClpS variants retain original N terminal amino acid specificity. Thermostable ClpS variants retain original N terminal amino acid affinity. ClpS affinity and selectivity depend on the second amino acid in the target peptide...
S1369703X1930378X
Estimations of the facility footprint and fixed capital investment of cell therapy facilities need to consider the unique features of the single use technologies selected for CT manufacture and the product nature that impacts scale out versus scale up approaches . A novel detailed factorial methodology is proposed for ...
Factorial methodology for fixed capital investment FCI of cell therapy facilities. Considers impact of single use technologies SUTs on facility design. Considers the product nature that impacts scale out versus scale up approaches. Benchmark values provided for cost and area factors for cell therapy facilities. Autolog...
S1369703X19303791
5 hydroxymethylfurfural is a versatile biomass derived chemical for synthesizing useful compounds . In this work an attempt is made to produce HMF by developing a low cost process for doing that using cellulosic waste and deep eutectic solvents . The most effective DES was choline chloride citric acid which provided a ...
The composition of wood dust and its byproducts from SE process were identified. The constituents of DESs affect the yield and selectivity of HMF was determined. The reaction conditions affect the yield and selectivity of HMF was explored. Optimal conditions for using pretreated wood dust to produce HMF were identified...
S1369703X19303808
The removal of atmospheric methane by methanotrophs is a potential strategy for mitigating global warming . However due to the low mass transfer of methane to methanotrophic cells the conventional bioprocesses require active gas supply with high energy consumption . This study aimed to evaluate methane degradation perf...
Freeze thaw treatment facilitated the immobilization of methanotrophic cells. Methane degradation is higher in microbial gas phase reactions even without agitation. Gel entrapment systems impaired methane degradation in the gas phase reaction. Absence of an aqueous diffusion barrier improved methane degradation efficie...
S1369703X1930381X
A lipase gene was identified and isolated from a fosmid metagenomics library constructed from forest topsoil samples . Error prone PCR and saturation mutagenesis were used to generate seven lipase variants S69P R194Q S69G S69P S69E S69P T99S N190S R194Q R194S and R194A by testing five different fatty acids of
Present study report engineering of a metagenome derived lipase gene. Positions R194 and S69 are identified as hot spot residues for improved activity. Reactivity of lipases can be engineered at positions away from the active site. Combining directed evolution with saturation mutagenesis is an effective approach.
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Since monoclonal antibodies are sensitive to the manufacturing process several mAb variants can be the result of a single batch production . The most critical source of heterogeneity is glycosylation which has a profound impact on safety and efficacy of the final product . Implementation of monitoring and control of th...
Monitoring of mAb glycosylation during CHO cell processes by. NIR probes. PLS regressions are limited for providing spectrum based glycosylation information. Consideration of the process nature in regression is critical for accurate monitoring. The novel use of LWR allowed to monitor total mAb concentration accurately....
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N acetyllactosamine is an important lactose derived molecule which can act as an effective prebiotic . In this study a process for the enzymatic synthesis and downstream purification of LacNAc was designed based on the use of thermostable galactosidases from
Techno economic analysis of large scale enzymatic production of N acetyllactosamine. Separation processes based on chromatography and crystallization were compared. The process based on selective crystallization and the BgaD D enzyme gave the lowest costs. Production capacity N acetylglucosamine recovery acceptor to do...
S1369703X19303997
In modern aquaculture simple and rapid methods of predicting fish ovulation are needed to produce seedlings in a stable and efficient manner . Ovulation time is variable due to environmental and physiological factors while 17 20 dihydroxy 4 pregnen 3 one an indicator of ovulation increases its concentration rapidly jus...
An amperometry immunosensor was developed for simple and fast monitoring 17 20 dihydroxy 4 pregnen 3 one DHP . The proposed sensor system is eco friendly because it used non toxic glucose as a source of sensor output. The sensor system may help us to predict fish ovulation which can improve the efficiency of modern aqu...
S1369703X19304000
In this study anaerobic membrane bioreactor was applied for the treatment of a model slurry of high strength organic solid waste . Continuous monitoring of reactor performances by chemical analyses and fine scale tracing of the AnMBR sludge microbiome by high throughput 16S rRNA gene sequencing were conducted during th...
Long term acclimatization of AnMBR sludge to treat organic solid waste was performed. SRT control to optimize MLSS in AnMBR improved reactor performances. High resolution dynamics of the AnMBR sludge microbiome were revealed. Constitution of methanogens was changed with the OLR increase and SRT control. Syntrophic meth...
S1369703X19304012
Environmental concerns and the depletion of fossil resources are the major factors that boost modern society towards bio based and circular economy . To this end the development of mathematical tools that can be used to perform rapid comparative analysis across multiple technology options is necessary . The aim of this...
A linear statistical model for comparing the economic performance of different bio based chemicals. Functional dependency of bioprocess economics on fermentation time titer and aeration rate. Fixed capital investment and utilities consumption of a biotransformation technology.
S1369703X19304036
We introduce a novel magnetically coupled mixer drive for biotechnological pharmaceutical and chemical applications requiring high grade aseptic conditions . The proposed design enables its application in larger volume bioreactors compared to traditional magnetic drives due to a possibility of introducing higher power ...
The design of the novel magnetically coupled mixer drive is demonstrated. Magnetic field simulations were performed for two magnetic drive scales. The magnetic mixers were built according to the simulated designs. Magnetic mixer performance was evaluated in terms of maximal torque and power input. The magnetic drive wa...
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To scale up a filling process in a cell manufacturing system the impact of the processing time on the final product quality should be evaluated . It is known that the suspended cells in a cryopreservation solution are subjected to various types of stress factors which eventually results in apoptotic or necrotic death ....
ROS accumulation induces apoptosis of cells suspended in cryopreservation solution. Treatment with antioxidant or at low temperature suppresses apoptosis induction. Low temperatures alone are sufficient to achieve maximal yield. Control of cellular redox balance is a key factor of a filling process system design.
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External magnetic field with simple rapid standardized and controllable characters can improve electricity harvesting in bioelectrochemical systems . Herein the fabrication of external magnetic field with microbial electrosynthesis system in which electrotrophic
Magnetic field stimulates. for more production of acetate in MES. Magnetic field induces. for more EPS and bacterial growth. Synergistic stimulating of magnetic field and circuital current for release of EPS. Additive effects of magnetic field and circuital current on. growth. Circuital current was more influential tha...
S1369703X19304073
The carbon release behaviour of polylactic acid starch blends and the correlation between solid phase denitrification performance and solid carbon decomposition were investigated by both batch experiments and numerical simulations . The results showed that the mass ratio of PLA to starch is a key parameter in determini...
Carbon release behavior of PLA starch based solid carbon was investigated. Mass ratio of the blends is a key parameter governing the TOC release rate. Hydrolysis contributed more to TOC released than the physicochemical leaching. Little TOC will accumulates in the effluent during the SPD process. The PLA starch blend i...
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Numerous micro physiological systems have been reported to successfully mimic the organ microenvironment . However there are currently only a few systems that focus on real time physiological monitoring for preclinical cytotoxicity assessment of drug candidates . We developed a multi sensor lung cancer on chip platform...
A lung cancer on chip platform was developed for real time physiological monitoring. All the biosensors were developed in house including pH and TEER impedance sensors. Transparent ITO electrode allowed for visual monitoring using 3D printed microscope. The toxicity of anticancer drugs doxorubicin and docetaxel was eva...
S1369703X19304218
The potential of Forward Osmosis technology to up concentrate succinic acid lactic acid and ethanol from fermentation broths was investigated . The aforementioned molecules were obtained from two residual resources
Succinic acid lactic acid and ethanol were produced from residual resources. Forward osmosis was examined to up concentrate fermentation products. Succinic acid concentration factor of 5.0 was achieved. Best results were obtained with NaCl 5.0M as draw solution. Water removals of up to 85 were attained.
S1369703X1930422X
Paper based diagnostics are rapid robust affordable and user friendly thus have potential for point of care . Modulation of sample flow in these technologies have the advantage of increased exposure between immunoreagents which ensures higher sensitivity and specificity . In this study common membrane types were compar...
Sample flow modulation in paper diagnostics increase exposure between immunoreagents that may increase sensor performance. Selection of membrane types and their modifications modulate sample flow and may increase the sensitivity of detection. Five different membranes were compared glassfiber polyester nitrocellulose po...
S1369703X19304231
In this work was presented a strategy to produce to concentrate and to apply a cocktail containing cell wall degrading enzymes . The novelties and the differences of this study from the others lie in the fact of defining the entire production process of a second generation biopesticide and in addition an enzyme cocktai...
High production of cell wall degrading enzymes. Membrane technology was efficient for enzyme enzymes concentration. Concentrated enzymes presented insecticidal activity.
S1369703X19304243
The work focuses on the bioelectrochemical treatment of wastewater containing phenol and trichlorophenol in microbial fuel cells with non coated and PANI SnO
Comparative bioremediation of mixed phenolic contaminants under anoxic and oxic conditions. PANI SnO. modified for the treatment of P TCP. Electrochemical polymerisation of PANI SnO. nanocomposite on the surface of carbon cloth electrode. Higher PD and COD removal efficiency for oxic treatment of P TCP.
S1369703X20300012
Butane is an abundant side product of oil and gas production and is mostly burned for energy and heat production . The alkane monooxygenase enzyme system
Volumetric productivity is driven by butane gas to liquid mass transfer. Gassing rate dominates volumetric productivity over pressure and temperature. Increasing butane content is no key to significantly rise volume productivity. a transferability demonstrated for different bubble column geometries.
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The assembly of multiple enzymes has received increasing attention due to the promising application in improving biocatalytic process . In this study supramolecular nanoreactors were engineered by assembly of polyphosphate kinase and bifunctional glutathione synthetase for adenosine triphosphate regeneration in vitro ....
Dimeric GshF and tetrameric family 2 PPK were self assembled into MECs through LZs mediated interaction. MECs were assembled into supramolecular MENRs driven by the substrate polyP. MENRs system showed higher ATP regeneration efficiency and stability than unassembled system. MENRs retained more than 70 of the initial a...
S1369703X20300036
Lycopene is an antioxidant that can be used as functional food or a high value product for nutraceutical pharmaceutical and cosmetic applications . In this paper the mevalonate and lycopene synthesis pathways were first built in
Biosynthesis of lycopene from metabolically engineered. Capable of using free fatty acids or waste cooking oil to improve lycopene yield. Co feeding with glucose and waste cooking oil to produce 2.7g L lycopene in 40h. Lycopene content in biomass 94mg g is among the highest levels reported so far.
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Suspended solids are one of major pollutants that deteriorate water quality . The high rate clarifier is commonly used as the tertiary treatment by coagulation to agglomerate particles thus achieving a high SS removal and making effluents acceptable for discharge . Currently the control of average residence time in ope...
Flow field and SS concentration were simulated in a full scale high rate clarifier. SS at the bottom of reaction tank was decreased by 35 to avoid SS sedimentation. Suitable under through channel and baffle heights were obtained by two phase model. The standard error between simulated and measured velocities was less t...
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The differentiation of human induced pluripotent stem cells into functional hepatocytes has the potential to solve the shortage of human primary liver cells and would be of use in drug screening . In this frame we developed a hiPSCs maturation strategy in microfluidic biochips using a liver on chip approach a promising...
Maturation of hiPSCs derived HLCs is improved by culture in a microfluidic biochip. The tissue formed presents liver specific markers such as Albumin CYP3A4 or the production of urea and cholesterol. Longer maturation might improve the functionality.
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This work aims to control foaming in a submerged membrane bioreactor by optimizing the organic loading rate and sludge retention time values to decrease the extracellular polymeric substance production used for the pharmaceutical wastewater treatment . Four lab scale SMBRs were operated for a period of more than 8 mont...
Quantity and quantify of foaming were evaluated at different SRTs and OLRs. Protein content of EPS can lead to more foam formation than carbohydrate. Foaming phenomenon can be controlled by optimizing OLR values. More OLR is not providing higher values of maximum specific growth rate m .
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genus is an important biological control agent . Most industrial conidia production processes are based on the use of plastic bags or containers containing 1kg of substrate . Static bioreactors such as packed columns trays and plastic bags are used for different scale conidia production . However the effect of aeration...
Conidia production increased threefold in aerated packed column bioreactor. Conidia productivity in columns were twice as high than those in trays and bags. Maximum conidia production was attained when the CO. production rate decreased 50 . Infectivity of conidia was independent of the aeration mechanisms tested.
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This study was carried out at both laboratory and pilot scale to investigate whether the presence of phosphorus affects the nitrification process during aerobic digestion of aquaculture aquaponic solid waste . Results from the laboratory scale aerobic digestions indicated that nitrification did not occur throughout the...
Phosphorus affects the bioconversion of organic solid waste into liquid fertilizer. Phosphorus delays the onset of nitrification of aquaculture aquaponic solid waste. Phosphorus should be avoided in bioprocessing of aquaculture aquaponic solid waste.
S1369703X20300097
Based on elementary flux mode analysis a novel approach is presented for monoclonal antibody production by GS CHO cells . A kinetic model is developed on the basis of a set of macro reactions which can predict the time dependent concentrations of metabolites cell growth and MAb productivity over a range of culture cond...
Cell culture kinetic modeling. Metabolic behavior under different culture conditions. The effect of glutamine availability on central carbon metabolism. Model based evaluation of fed batch processes.
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Changes in microbial communities are observed during the long term operation of activated sludge systems employing an excess sludge reduction technology . Short term changes are also significant to confirm if key microbes are damaged but they have not been investigated due to the absence of an appropriate method . We r...
A sludge reduction method to damage and identify prokaryotes was proposed. A high pressure jet device HPJD was applied for sludge reduction. Eluted DNA from damaged bacteria was sequenced for taxonomic identification. Nitrifying bacteria were not damaged by HPJD treatment. Protozoa were severely damaged by HPJD treatme...
S1369703X20300127
CdSe quantum dots are semiconductor materials and possess unique optical and electronic properties therefore being increasingly used in many fields . Biosynthesis of CdSe QDs has several advantages over the chemical synthesis route . In this study the CdSe QDs were biosynthesized using a yeast
CdSe quantum dots was synthesized by. PA 1 with small size and a narrow size distribution. The concentration of Cd determine CdSe biosynthesis that is a detoxification strategy of Cd in. PA 1. Bio synthesized CdSe quantum dots showed photocatalytic activity toward MG degradation under ultraviolet and visible light.
S1369703X20300139
Thalassaemia is an inherited blood disorder with serious complications . Combining the unique advantages of DNA and magnetoelastic materials an ME DNA biosensor was proposed that can wirelessly detect a target DNA sequence that is a 4 bp deletion in codon 41 42 in the globin gene causing thalassaemia . The thiolated ca...
An ME DNA biosensor was developed to detect a common mutated DNA causing thalassaemia. sDNA AuNPs serve as the signal amplifier. The sandwich type structure enables label free detection. A low detection limit of 0.571pM and high sensitivity of 72.7Hz nM were obtained. The DNA biosensor exhibits excellent sensitivity se...
S1369703X20300140
TCCC 13007 was used to produce aminobutyric acid . The fermentation broth was degermed decolorized and deionized before the green style spray drying and the process parameters were optimized . Single factor experiments were carried out to optimize 7 factors to investigate their effects on spray drying . Maltodextrin wa...
GABA rich powder was prepared from fermentation broth by green style spray drying. Maltodextrin was screened out as best drying aid to help spray drying. The 7 parameters of spray drying were optimized by response surface methodology. The obtained results lightened cleaner GABA preparation for industrial fermentation.
S1369703X20300152
Due to the availability of natural gas shale gas and flared gas there is increased interest in converting methane in these gases into commodity chemicals via cost effective and sustainable processes . Recently we have demonstrated an efficient process concept converting methane to lactic acid by methanotrophic bacteria...
Four different scenarios of BioGTLA were analyzed in the n. plant. Productivity titer and CCE are identified as the key cost drivers for MSP. A promising MSP of 2.17 kg can be realized in a long term scenario. A preliminary LCA was performed to show environmental considerations.
S1369703X20300164
The textile dyeing and printing industry has led to extensive environmental pollution and severely threatens ecosystems . Immobilized laccase is an effective biocatalyst for the biotreatment of dye effluents but is usually restricted by its aerobic requirements . Thus it is desirable to design an efficient reactor that...
An HRR reactor was designed to satisfy the oxygen demand of catalysis of dye by BNC immobilized laccase. Decolourization efficiency of Reactive Blue 19 dye with laccase was compared in reactors HRR and VMR. HRR provides immobilized laccase better thermostability higher oxygen availability and larger contact reacting ar...
S1369703X20300176
Carboxylic acids are high added value compounds that can be produced via anaerobic fermentation by using agroindustrial residues as substrates . However different compounds in wastewater impose uncontrolled metabolic pathways in which the acidogenic fermentation kinetics need to be elucidated . This work aimed to asses...
Dairy wastewater DW is a potential substrate to produce carboxylic acids CA . Kinetic modeling is a useful tool to elucidate acidogenic fermentation kinetics. High yield of CA 0.66 mgCA mgCOD. was obtained from DW acidogenic fermentation. Models that describe an exponential phase are suitable to simulate CA production....