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As an extremophile resource, functional Haloarchaea strains are extremely time-consuming to screen. Here, taking the screening of low-salt-tolerant strains as an example, based on the qPCR assays that shortened time by 4-7 times and achieved 100 % accuracy, a universal strategy for rapid and accurate screening of functional Haloarchaea strains was established.

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Ammonia loss is the most severe during the high-temperature stage (>50°C) of aerobic composting. Regulating ammonia volatilization during this period via thermophilic microbes can significantly improve the nitrogen content of compost and reduce air pollution due to ammonia loss. In this study, an ammonia-assimilating bacterial strain named LL-8 was screened out as having the strongest ammonia nitrogen conversion rate (32.7%) at high temperatures (50°C); it is able to significantly reduce 42.9% ammonia volatile loss in chicken manure composting when applied at a high-temperature stage. Phylogenetic analysis revealed that LL-8 was highly similar (>98%) with Priestia aryabhattai B8W22T and identified as Priestia aryabhatta. Genomic analyses indicated that the complete genome of LL-8 comprised 5,060,316 base pairs with a GC content of 32.7% and encoded 5,346 genes. Genes, such as gudB, rocG, glnA, gltA, and gltB, that enable bacteria to assimilate ammonium nitrogen were annotated in the LL-8 genome based on the comparison to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The results implied that the application of thermophilic ammonia-assimilating strain P. aryabhatta LL-8 would be a promising solution to reduce ammonia loss and mitigate air pollution of aerobic composting.IMPORTANCEAerobic composting is one of the essential ways to recycle organic waste, but its ammonia volatilization is severe and results in significant nitrogen loss, especially during the high-temperature period, which is also harmful to the environment. The application of thermophilic bacteria that can use ammonia as a nitrogen source at high temperatures is helpful to reduce the ammonia volatilization loss of composting. In this study, we screened and identified a bacteria strain called LL-8 with high temperature (50°C) resistance and strong ammonia-assimilating ability. It also revealed significant effects on decreasing ammonia volatile loss in composting. The whole-genome analysis revealed that LL-8 could utilize ammonium nitrogen by assimilation to decrease ammonia volatilization. Our work provides a theoretical basis for the application of this functional bacteria in aerobic composting to control nitrogen loss from ammonia volatilization.

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The economical and efficient commercial production of second-generation bioethanol requires fermentation microorganisms capable of entirely and rapidly utilizing all sugars in lignocellulosic hydrolysates. In this study, we developed a recombinant Saccharomyces cerevisiae strain, BLH510, through protoplast fusion and metabolic engineering to enhance its ability to co-ferment glucose, xylose, cellobiose, and xylooligosaccharides while tolerating various inhibitors commonly found in lignocellulosic hydrolysates. The parental strains, LF1 and BLN26, were selected for their superior glucose/xylose co-fermentation capabilities and inhibitor tolerance, respectively. The fusion strain BLH510 demonstrated efficient utilization of mixed sugars and high ethanol yield under oxygen-limited conditions. Under low inoculum conditions, strain BLH510 could completely consume all four kinds of sugars in the medium within 84 h. The fermentation produced 33.96 g/L ethanol, achieving 84.3% of the theoretical ethanol yield. Despite the challenging presence of mixed inhibitors, BLH510 successfully metabolized all four sugars above after 120 h of fermentation, producing approximately 30 g/L ethanol and reaching 83% of the theoretical yield. Also, strain BLH510 exhibited increased intracellular trehalose content, particularly under conditions with mixed inhibitors, where the intracellular trehalose reached 239.3 mg/g yeast biomass. This elevated trehalose content contributes to the enhanced stress tolerance of BLH510. The study also optimized conditions for protoplast preparation and fusion, balancing high preparation efficiency and satisfactory regeneration efficiency. The results indicate that BLH510 is a promising candidate for industrial second-generation bioethanol production from lignocellulosic biomass, offering improved performance under challenging fermentation conditions. Our work demonstrates the potential of combining protoplast fusion and metabolic engineering to develop superior S. cerevisiae strains for lignocellulosic bioethanol production. This approach can also be extended to develop robust microbial platforms for producing a wide array of lignocellulosic biomass-based biochemicals.

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BACKGROUND: Fucoxanthin has been widely investigated owing to its beneficial biological properties, and the model diatom Phaeodactylum tricornutum, possessing fucoxanthin (Fux) chlorophyll proteins as light-harvesting systems, is considered to have the potential to become a commercial cell factory for the pigment production. RESULTS: Here, we compared the pigment contents in 10 different P. tricornutum strains from the globe, and found that strain CCMP631 (Pt6) exhibited the highest Fux content but with a low biomass. Comparison of mRNA levels revealed that higher Fux content in Pt6 was related with the higher expression of gene violaxanthin de-epoxidase-like (VDL) protein 1 (VDL1), which encodes the enzyme catalyzing the tautomerization of violaxanthin to neoxanthin in Fux biosynthesis pathway. Single nucleotide variants of VDL1 gene and allele-specific expression in strains Pt1 (the whole genome sequenced strain CCMP632) and Pt6 were analyzed, and overexpressing of each of the 4 VDL1 alleles, two from Pt1 and two from Pt6, in strain Pt1 leads to an increase in downstream product diadinoxanthin and channels the pigments towards Fux biosynthesis. All the 8 VDL1 overexpression (OE) lines showed significant increases by 8.2 to 41.7% in Fux content without compromising growth, and VDL1 Allele 2 OE lines even exhibited the higher cell density on day 8, with an increase by 24.2-28.7% in two Pt1VDL1-allele 2 OE lines and 7.1-11.1% in two Pt6VDL1-allele 2 OE lines, respectively. CONCLUSIONS: The results reveal VDL1, localized in the plastid stroma, plays a key role in Fux over-accumulation in P. tricornutum. Overexpressing VDL1, especially allele 2, improved both the Fux content and growth rate, which provides a new strategy for the manipulation of Fux production in the future.

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Recent advances in messenger ribonucleic acid (mRNA) vaccines and gene therapy vectors have increased the need for rapid plasmid DNA (pDNA) screening and production within the biopharmaceutical industry. High-throughput (HT) fermentor systems, such as the Ambr® 250 HT, can significantly accelerate process development timelines of pDNA upstream processes compared to traditional bench-scale glass fermentors or small-scale steam-in-place (SIP) fermentors. However, such scale-down models must be qualified to ensure that they are representative of the larger scale process similar to traditional small-scale models. In the current study, we developed a representative scale-down model of a Biostat® D-DCU 30 L pDNA fermentation process in Ambr® 250 HT fermentors using three cell lines producing three different constructs. The Ambr scale-down model provided comparable process performance and pDNA quality as the 30 L SIP fermentation process. In addition, we demonstrated the predictive value of the Ambr model by two-way qualification, first by accurately reproducing the prior trends observed in a 30 L process, followed by predicting new process trends that were then successfully reproduced in the 30 L process. The representative and predictive scale-down Ambr model developed in this study would enable a faster and more efficient approach to strain/clone/host-cell screening, pDNA process development and characterization studies, process scale-up studies, and manufacturing support.

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BACKGROUND: Care givers of Palliated patients are at risk of adverse physical, psychosocial and emotional sequelae in varied nature. Efficient and valid assessment tools facilitate early detection to take corrective measures. The Modified Caregiver Strain Index (MCSI), composed of domains associated with caregiver strain is a simple and brief tool that can be used in both clinical and field settings. This study aimed to adapt and validate this in order to cater effective palliative care services in Sri Lanka. METHODS: After cross-cultural adaptation, 200 primary caregivers in 3 teaching hospitals were recruited. The internal consistency, item-total correlations, of the 13-item S-MCSI were performed. The criterion validity was assessed by Pearson correlation between the total scores of S-MCSI, the Karnofky Performance Scale and the Barthel index. Construct validity was determined by the principal component analysis keeping the Varimax with Keiser normalization as the rotation method. The Kaiser-Meyer-Olkin test (KMO) and Bartlett's test of sphericity statistics were also performed to determine the adequacy of the sample and correlations between items, respectively. The number of factors was determined by the Scree plot, percentage of variance explained by each component and number of Eigen values over 01 (Kaiser-Guttman rule). RESULTS: The total MCSI score ranged 0 to 26. The overall Cronbach's alpha of the 13-item questionnaire was 0.80 while item-total corrections ranged 0.34 to 0.62, exception of one item (0.11). Inverse correlations were demonstrated in total scores of MCSI and Karnofky Performance Scale (r =- 0.32, p < 0.001) and Barthel index (r =-0.34, P < 0.001). A Kaiser-Meyer-Olkin value of 0.79 (p < 0.001) for Bartlett's test indicated adequate sampling and nonlinearity of factors. The Scree plot showed a three-factor structure explaining 57% of the variation. Items regarding personal wellbeing of caregiver loaded together while the effects on the family loaded separately. Adjustment of personal concerns and family issues along with time alteration grouped as the third factor. CONCLUSIONS: The study showed that the Sinhala version of MCSI has adequate psychometric properties and reliability to be used as a validated tool to estimate the caregiver burden within a short time period for any health care workers.

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Compelling evidence has tightly linked gut microbiota with host metabolism homeostasis and inspired novel therapeutic potentials against metabolic diseases (e.g., hyperlipidemia). However, the regulatory profile of individual bacterial species and strain on lipid homeostasis remains largely unknown. Herein, we performed a large-scale screening of 2250 human gut bacterial strains (186 species) for the lipid-decreasing activity. Different strains in the same species usually displayed distinct lipid-modulatory actions, showing evident strain-specificity. Among the tested strains, Blautia producta exhibited the most potency to suppress cellular lipid accumulation and effectively ameliorated hyperlipidemia in high fat diet (HFD)-feeding mice. Taking a joint comparative approach of pharmacology, genomics and metabolomics, we identified an anteiso-fatty acid, 12-methylmyristic acid (12-MMA), as the key active metabolite of Bl. Producta. In vivo experiment confirmed that 12-MMA could exert potent hyperlipidemia-ameliorating efficacy and improve glucose metabolism via activating G protein-coupled receptor 120 (GPR120). Altogether, our work reveals a previously unreported large-scale lipid-modulatory profile of gut microbes at the strain level, emphasizes the strain-specific function of gut bacteria, and provides a possibility to develop microbial therapeutics against hyperlipidemia based on Bl. producta and its metabolite.

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As a semi-essential amino acid, l-arginine (l-Arg) plays an important role in food, health care, and medical treatment. At present, the main method of producing l-Arg is the use of microbial fermentation. Therefore, the selection and breeding of high-efficiency microbial strains is the top priority. To continuously improve the l-Arg production performance of the strains, a series of metabolic engineering strategies have been tried to transform the strains. The production of l-Arg by metabolically engineered Corynebacterium glutamicum (C. glutamicum) reached a relatively high level. Escherichia coli (E. coli), as a strain with great potential for l-Arg production, also has a large number of research strategies aimed at screening effective E. coli for producing l-Arg. E. coli also has a number of advantages over C. glutamicum in producing l-Arg. Therefore, it is of great significance to screen out excellent and stable E. coli to produce l-Arg. Here, based on recent research results, we review the metabolic pathways of l-Arg production in E. coli, the research progress of l-Arg production in E. coli, and various regulatory strategies implemented in E. coli.

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Aromatic volatile organic compounds (VOCs) are a type of common pollution form in chemical contaminated sites. In this study, seven aromatic VOCs such as benzene, toluene, ethylbenzene, chlorobenzene, m-xylene, p-chlorotoluene and p-chlorotrifluorotoluene were used as the only carbon source, and four strains of highly efficient degrading bacteria were screened from the soil of chemical contaminated sites, then the synthetic bacterial consortium was constructed after mixing with an existing functional strain (Bacillus benzoevorans) preserved in the laboratory. After that, the synthetic bacterial consortium was used to explore the degradation effect of simulated aromatic VOCs polluted wastewater. The results showed that the functional bacterium could metabolize with aromatic VOCs as the only carbon source and energy. Meanwhile, the growth of the synthetic bacterial consortium increased with the additional carbon resources and the alternative of organic nitrogen source. Ultimately, the applicability of the synthetic bacterial consortium in organic contaminated sites was explored through the study of broad-spectrum activity.

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In this study, a quality evaluation model of fermented kiwifruit juice (KJ) based on strain growth characteristics, sensory quality and functional characteristics was established by PCA, and the effects of mono- and mixed culture fermentation on the sensory and aroma profiles of KJ were comparatively studied. Experiments determined that L. brevis (LB) was the optimal strain for monoculture fermentation, and L. plantarum (LP2):LB = 1:2 was the optimum ratio for mixed fermentation. The results showed that lactic acid bacteria (LAB) fermentation significantly reduced the pH, soluble solid content and lightness, and improved its functional characteristics and viscosity. Mixed culture fermentation was superior to monoculture fermentation in terms of colony counts, sensory quality and viscosity. In general, after LAB fermentation, the concentrations of esters, ketones, alcohols and terpenoids in KJ increased significantly, while the concentrations of aldehydes decreased significantly. The production of esters and terpenoids was more strongly promoted by monoculture fermentation, while mixed culture fermentation promoted the production of more ketones and alcohols. 2,5-octanedione and 1-octen-3-ol could be the characteristic aroma compounds of mixed fermented KJ.

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In recent years, the utilization of antibiotics in animal feed has been restricted, probiotics have been increasingly used to replace antibiotics in maintaining animal health. The aim of this study was to screen and evaluate probiotics with excellent probiotic potential from the gut of healthy goslings for clinical application. Thirteen strains of Bacillus (named AH-G201 to AH-G2013), including 2 strains of Bacillus subtilis (B. subtilis), 6 strains of Bacillus licheniformis (B. licheniformis) and 5 strains of Bacillus amyloliquefaciens (B. amyloliquefaciens), were isolated and identified. Then, acid and bile salts tolerance tests were performed to screen probiotics strains that could survive under different environments. The effects of screened probiotics on the growth of pathogenic Escherichia coli (E. coli) and Salmonella were assessed. Furthermore, we performed the drug resistance tests and safety tests in animals. The results showed that B. Subtilis AH-G201, B. licheniformis AH-G202 and AH-G204 exhibited higher gastrointestinal resistance under in vitro conditions, and showed a moderate level of resistance to the tested antibiotics. Importantly, AH-G201 and AH-G202 showed 24 to 60% inhibition rate against pathogenic E. coli and Salmonella. Moreover, the safety analysis of AH-G201 and AH-G202 suggested that the 2 probiotics strains have no adverse effects on body weight gain and feed intake in the broilers, and in addition, they have significantly improved growth performance. Finally, we analyzed effects of B. Subtilis AH-G201and B. licheniformis AH-G202 on growth performance, immune organ index and the feces microbes of broilers. The results showed that broilers fed with high doses (5 × 109 CFU/mL, for single strain) of a mixture of AH-G201 and AH-G202 exhibited good growth performance, and exhibited the greatest gain in spleen weight and the highest lactic acid bacteria counts. These findings indicate that the combined addition of B. Subtilis AH-G201 and B. licheniformis AH-G202 has the potential to replace antibiotics and to improve the growth performance of broilers.

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In order to discover a broad-specificity and high stability chitinase, a marine fungus, Aspergillus fumigatus df347, was identified in the sediments of mangrove wetlands in Qinzhou Bay, China. The chitinase gene (AfChi28) from A. fumigatus df347 was cloned and heterologously expressed in Escherichia coli, and the recombinant enzyme AfChi28 was purified and characterized. AfChi28 is an acido-halotolerant- and temperature-resistant bifunctional enzyme with both endo- and exo-cleavage functions. Its enzymatic products are mainly GlcNAc, (GlcNAc)2, (GlcNAc)3 and (GlcNAc)4. Na+, Mg2+, K+, Ca2+ and Tris at a concentration of 50 mM had a strong stimulatory effect on AfChi28. The crude enzyme and pure enzyme exhibited the highest specific activity of 0.737 mU/mg and 52.414 mU/mg towards colloidal chitin. The DxDxE motif at the end of strand ß5 and with Glu154 as the catalytic residue was verified by the AlphaFold2 prediction and sequence alignment of homologous proteins. Moreover, the results of molecular docking showed that molecular modeling of chitohexaose was shown to bind to AfChi28 in subsites -4 to +2 in the deep groove substrate-binding pocket. This study demonstrates that AfChi28 is a promising chitinase for the preparation of desirable chitin oligosaccharides, and provides a foundation for elucidating the catalytic mechanism of chitinases from marine fungi.

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Biological valorization of lignin to bioplastics is a promising route to improve biorefinery efficiency and address environmental challenges. A two-stage screening procedure had been designed to successfully identify four ligninolytic bacteria from soil samples. The isolated bacteria displayed substrate preference of guaiacyl- and hydroxyphenyl-based aromatics, but they effectively synthesized polyhydroxyalkanoates (PHAs). B. cepacia B1-2 and P. putida KT3-1 accumulated 27.3% and 20.9% PHA in cells and achieved a titer of 280.9 and 204.1 mg/L, respectively, from p-hydroxybenzoic acid. The isolated bacteria exhibited good ligninolytic performance indicated by the degradation of ß-O-4 linkage and small molecules. B. cepacia B1-2 grew well on actual lignin substrate and yielded a PHA titer of 87.2 mg/L. With the design of fed-batch mode, B. cepacia B1-2 produced the highest PHA titer of 1420 mg/L from lignin-derived aromatics. Overall, isolated ligninolytic bacteria show good PHA accumulation capacity, which are the promising host strains for lignin valorization.

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The uncontrolled incorporation of non-canonical branched chain amino acids (ncBCAAs) such as norleucine, norvaline and ß-methylnorleucine into recombinant proteins in E. coli production processes is a crucial problem in the pharmaceutical industry, since it can lead to the production of altered proteins with non-optimal characteristics. Despite various solutions, to date there are no engineered strains that exhibit a reduced accumulation of these ncBAAs. In this study, novel E. coli K-12 BW25113 strains with exogenous tunable expression of target genes of the BCAA biosynthetic pathway were developed. For this purpose, single gene knock-outs for thrA, ilvA, leuA, ilvIH, ilvBN, ilvGM and ilvC were complemented with plasmids containing the respective genes under control of an arabinose promoter. These clones were screened in a mL-bioreactor system in fed-batch mode under both standard cultivation conditions and with pyruvate pulses, and induction of a min-proinsulin. Screening was performed by comparing the impurity profile of the recombinant mini-proinsulin expressed of each clone with the E. coli BW25113 WT strain, and the most promising clones were cultivated in a 15L Screening showed that up-regulation of ilvC, ilvIH and ilvGM, and downregulation of leuA and ilvBN trigger a reduction of norvaline and norleucine accumulation and misincorporation into mini-proinsulin. The stirred tank bioreactor cultivations confirmed that up-regulation of ilvIH and ilvGM were most effective to reduce the ncBCAA misincorporation. This novel approach for a reduced ncBCAA misincorporation may be solution to this old challenging problem in the large-scale production of human therapeutics.

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Lytic polysaccharide monooxygenases (LPMOs) are copper-dependent enzymes, which can catalyze the oxidative cleavage of polysaccharide ß-1,4 glycosidic bonds to improve the hydrolysis efficiency of the substrate by other glycoside hydrolases. To improve the conversion efficiency of cellulose and chitin, a strain was screened from the soil of Yuelu Mountain in Hunan province, China. The gene sequence of a novel AA10 LPMO (BaLPMO10) was successfully cloned from the genome of the strain and heterologously expressed in E. coli BL21 (DE3). The optimal enzyme activity of BaLPMO10 was observed at pH 6.0 and 70 °C using 2,6-dimethoxyphenol as substrate, and its maximum specific activity was 91.4 U/g. When BaLPMO10 synergized with glycoside hydrolase to degrade microcrystalline cellulose and colloidal chitin, the reducing sugar content increased by 7% and 23%, respectively, compared to glycoside hydrolase alone. Moreover, the results of molecular docking and molecular dynamics simulation showed that the distance between BaLPMO10 and cellohexaose were further than that of BaLPMO10 and chitohexaose, and the number of hydrogen bonds between BaLPMO10 and cellohexaose were lower than that of BaLPMO10 and chitohexaose. Finally, the hot spot residues of BaLPMO10 interacting with chitohexaose/cellohexaose were identified.

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"Lianzhifan solution" (LZF) is produced by the natural fermentation of coptis root and gardenia fruit, and it is a classic prescription for external use in anorectal department. During the fermentation process, the structural evolution of microbial communities led to significant changes in the chemical profile. In this study, we first analyzed the dynamic changes of chemical components as well as the composition and succession of microbial community during the whole fermentation process of LZF, and confirmed the changes of characteristics of nine compounds during the whole fermentation process by metabolic profile. Further analysis found that there was no significant change of alkaloids in all stages of fermentation of LZF, but there were significant changes of iridoids in the middle and late stage of fermentation by deglycosylation. Genipin gentiobioside and geniposide were converted to genipin by biotransformation, showing that deglycosylation was the main event occurring in the fermentation. The community composition and abundance of species in 10 and 19days LZF fermentation broth were analyzed with high-throughput sequencing technology, and 16 dominant bacterial genera and 15 dominant fungal genera involved in the fermentation process were identified. Correlation analysis revealed that Penicillium expansum and Aspergillus niger involved in the fermentation were the dominant genera closely related to the dynamic changes of the deglycosylation of the main chemical components, and P. expansum YY-46 and A. niger YY-9 strains were obtained by the further fractionation. Then the monoculture fermentation process was evaluated, whereby we found that the deglycoside conversion rate of iridoid glycosides was greatly improved and the fermentation cycle was shortened by 3-4 times. This finding combined with equivalence evaluation of chemical component and pharmacodynamics to confirm that P. expansum YY-46 and A. niger YY-9 strains were key strains for fermentation concoction. This study established an efficient and practical screening strategy "Microfauna communities-Chemical component-Pharmacodynamic" axis for key strain, to improve the production process and formulating good manufacturing practice (GMP) work, and it is also applicable to the whole fermentation drugs industry. Graphical AbstractThe figure highly summarizes the research content of this study and shows the screening process of key strains in LZF fermentation.

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Electrolytic manganese residue (EMR) is a kind of solid waste with a high silicon content. Most of the silicon in EMR, however, exist in the state of SiO2, which cannot be directly absorbed by plants. Currently, it is very challenge to recover the silicon from EMR. In this study, a preliminary screening of strains with silicon-activating ability was conducted, and four strains were screened out and isolated from the soil around the tailings pond of EMR. Then, single factor experiments were conducted to obtain the optimal growth conditions of the four strains, and the results indicated that the Ochrobactrum sp. T-07 had the best silicon-activating ability from EMR after nitrosoguanidine mutagenesis (Ochrobactrum sp. T-07-B). The available silicon (in terms of SiO2) in the leaching solution was up to 123.88 mg L-1, which was significantly higher than that produced by Bacillus circulans and Paenibacillus mucilaginosus, the two commercial available pure culture strains. Results of direct/indirect contact experiments between Ochrobactrum sp. T-07-B and EMR revealed that bioleaching was promoted under the synergistic effect of bacteria growth on the surface of and metabolism within EMR. The newly isolated strains with silicon-activating effect are different from the existing-known silicate bacteria and may be used for more efficient silicon activation in silicate minerals.

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Insufficient mixing in large-scale bioreactors provokes gradient zones of substrate, dissolved oxygen (DO), pH, and other parameters. E. coli responds to a high glucose, low oxygen feeding zone with the accumulation of mixed acid fermentation products, especially formate, but also with the synthesis of non-canonical amino acids, such as norvaline, norleucine and ß-methylnorleucine. These amino acids can be mis-incorporated into recombinant products, which causes a problem for pharmaceutical production whose solution is not trivial. While these effects can also be observed in scale down bioreactor systems, these are challenging to operate. Especially the high-throughput screening of clone libraries is not easy, as fed-batch cultivations would need to be controlled via repeated glucose pulses with simultaneous oxygen limitation, as has been demonstrated in well controlled robotic systems. Here we show that not only glucose pulses in combination with oxygen limitation can provoke the synthesis of these non-canonical branched-chain amino acids (ncBCAA), but also that pyruvate pulses produce the same effect. Therefore, we combined the enzyme-based glucose delivery method Enbase® in a PALL24 mini-bioreactor system and combined repeated pyruvate pulses with simultaneous reduction of the aeration rate. These cultivation conditions produced an increase in the non-canonical branched chain amino acids norvaline and norleucine in both the intracellular soluble protein and inclusion body fractions with mini-proinsulin as an example product, and this effect was verified in a 15 L stirred tank bioreactor (STR). To our opinion this cultivation strategy is easy to apply for the screening of strain libraries under standard laboratory conditions if no complex robotic and well controlled parallel cultivation devices are available.

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Tetracarbon organic acids are important platform chemicals that are widely used in the food, chemical, medicine, material industries and agriculture. Compared with the traditional petrochemical process, the production of tetracarbon organic acids by microbial fermentation is more promising due to milder reaction conditions, greener process and better environmental compatibility. This review summarizes the biosynthetic pathways and metabolic mechanisms for the production of tetracarbon organic acids, and illustrates recent advances, challenges, and future perspectives in the production of tetracarbon organic acids by naturally selected or purposefully engineered strains.

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Tetracarbon organic acids are important platform chemicals that are widely used in the food, chemical, medicine, material industries and agriculture. Compared with the traditional petrochemical process, the production of tetracarbon organic acids by microbial fermentation is more promising due to milder reaction conditions, greener process and better environmental compatibility. This review summarizes the biosynthetic pathways and metabolic mechanisms for the production of tetracarbon organic acids, and illustrates recent advances, challenges, and future perspectives in the production of tetracarbon organic acids by naturally selected or purposefully engineered strains.

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