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2-羟基丁酸
ADVANCED SYNTHESIS & CATALYSIS · 2016 ·Vol. 358 ·期 18 ·2923-2928 · IF 6.453

Efficient Biosynthesis of (R)- or (S)-2-Hydroxybutyrate from l-Threonine through a Synthetic Biology Approach

Peiyuan Yao,Yunfeng Cui,Shanshan Yu,Yuncheng Du,Jinhui Feng,Qiaqing Wu,Dunming Zhu

An efficient multi-enzyme cascade reaction for the synthesis of ( R )- or ( S )-2-hydroxybutyric acid [( R )- or ( S )-2-HB] from l -threonine was developed by using recombinant Escherichia coli cells expressing separately or co-expressing l -threonine deaminase from Escherichia coli K-12 ( ilvA ), formate dehydrogenase (FDH) from Candida boidinii and l -lactate dehydrogenase ( l -LDH) from Oryctolagus cuniculus or d -lactate dehydrogenase ( d -LDH) from Staphylococcus epidermidis ATCC 12228. Up to 750 mM of l -threonine were completely transformed to ( R )- or ( S )-2-HB in optically pure form (>99% ee ) with high isolated yields. This one-pot multi-enzyme transformation provides a new practical method for the synthesis of these important optically pure compounds.

CAS / MDL: 72-19-5
研究领域: 生物化学 · 合成生物学 · 代谢工程
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Metabolites · 2023 ·Vol. 13 ·期 3 ·451 · IF 4.1

2 Hydroxybutyric Acid-Producing Bacteria in Gut Microbiome and Fusobacterium nucleatum Regulates 2 Hydroxybutyric Acid Level In Vivo

Fujian Qin,Jiankang Li,Tianxiao Mao,Shuo Feng,Jing Li,Maode Lai

2-hydroxybutyric acid (2HB) serves as an important regulatory factor in a variety of diseases. The circulating level of 2HB in serum is significantly higher in multiple diseases, such as cancer and type 2 diabetes (T2D). However, there is currently no systematic study on 2HB-producing bacteria that demonstrates whether gut bacteria contribute to the circulating 2HB pool. To address this question, we used BLASTP to reveal the taxonomic profiling of 2HB-producing bacteria in the human microbiome, which are mainly distributed in the phylum Proteobacteria and Firmicutes. In vitro experiments showed that most gut bacteria (21/32) have at least one path to produce 2HB, which includes Aspartic acid, methionine, threonine, and 2-aminobutyric acid. Particularly,Fusobacterium nucleatumhas the strongest ability to synthesize 2HB, which is sufficient to alter colon 2HB concentration in mice. Nevertheless, neither antibiotic (ABX) norFusobacterium nucleatumgavage significantly affected mouse serum 2HB levels during the time course of this study. Taken together, our study presents the profiles of 2HB-producing bacteria and demonstrates that gut microbiota was a major contributor to 2HB concentration in the intestinal lumen but a relatively minor contributor to serum 2HB concentration.Keywords:2-hydroxybutyric acid;gut microbiota;HMP;taxonomic identification;Fusobacterium nucleatum

研究领域: 微生物学 · 分子生物学 · 医学研究
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ENVIRONMENTAL SCIENCE & TECHNOLOGY · 2023 · IF 11.4

Insights into C–C Bond Cleavage Mechanisms in Dichloroacetonitrile Formation during Chlorination of Long-Chain Primary Amines, Amino Acids, and Dipeptides

Yingying Zhou,Jia-jia Jiao,Huang Huang,Yong Dong Liu,Rugang Zhong,Xin Yang

Dichloroacetonitrile (DCAN) as one of the potentially prioritized regulated DBPs has drawn great attention; however, understanding its formation, especially the C–C bond cleavage mechanisms, is limited. In this study, DCAN formation mechanisms from long-chain primary amines, amino acids, and dipeptides during chlorination were investigated by a combined computational and experimental approach. The results indicate that nitriles initially generate for all of the above precursors, then they undergo β-C-hydroxylation or/and α-C-chlorination processes, and finally, DCAN is produced through the Cα–Cβ bond cleavage. For the first time, the underlying mechanism of the C–C bond cleavage was unraveled to be electron transfer from the O– anion into its attached C atom in the chlorinated nitriles, leading to the strongly polarized Cα–Cβ bond heterocleavage and DCAN– formation. Moreover, DCAN molar yields of precursors studied in the present work were found to be determined by their groups at the γ-site of the amino group, where the carbonyl group including −CO2–, −COR, and −CONHR, the aromatic group, and the −OH group can all dramatically facilitate DCAN formation by skipping over or promoting the time-consuming β-C-hydroxylation process and featuring relatively lower activation free energies in the C–C bond cleavage. Importantly, 4-amino-2-hydroxybutyric acid was revealed to possess the highest DCAN yield among all the known aliphatic long-chain precursors to date during chlorination. Additionally, enonitriles, (chloro-)isocyanates, and nitriles can be generated during DCAN formation and should be of concern due to their high toxicities.

CAS / MDL: 13477-53-7
研究领域: 环境化学 · 水处理 · 毒理学
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LWT-FOOD SCIENCE AND TECHNOLOGY · 2021 · IF 4.952

In vitro fermentation of chitooligosaccharides and their effects on human fecal microbial community structure and metabolites

Xiao-Guo Ji,Kun-Lin Chang,Mai Chen,Liang-Liang Zhu,Arwa Osman,Hao Yin,Li-Ming Zhao

Chitooligosaccharides (COS), with a specific degree of polymerization, were evaluated for their effect on human fecal microbiota, as well as their metabolite, using an in vitro anaerobic batch fermentation model. COS increased the richness and diversity of the gut microbial community. More importantly, the microbial community structure of the COS groups was significantly different from the control and fructooligosaccharides (FOS) groups. COS specifically enriched the butyric and propionic acid-producing microbiota and targeted Faecalibacterium , Clostridium_sensu_stricto_1 , C._sensu_stricto_13 , and Fusicatenibacter . Furthermore, COS increased the acetic, propionic, and butyric acid contents. The production of propionic acid was greater than that obtained using FOS. Metabolome analysis suggested that COS could upregulate allocholic acid, 1,3-butanediol, 3,4-dihydroxybutanotic acid, and 2-hydroxybutyric acid production and downregulate putrescine, ethanamine, hexanoic acid, and branched chain amino acid ( l -valine and l -leucine) production in the fermentation broth. These differential metabolites were closely related to lipid, glucose, and amino acid metabolism. These results should inform further development of COS as potential raw materials for functional foods and health products.

研究领域: 微生物学 · 营养学 · 胃肠病学 · 食品科学 · 代谢组学
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