title: Metabolic pathway optimization for biosynthesis of 1,2,4-butanetriol from xylose by engineered Escherichia coli.
abstract: 1,2,4-Butanetriol (BT) and related derivatives have been widely used in many fields, especially in the military and in medicine. In this paper, we systematically optimized the BT biosynthetic pathway. We first investigated the activities of various NADH dependent aldehyde reductases (ALRs), which catalyze the fourth reaction in the four-step pathway for BT production from xylose in E. coli, and found that a combination of multiple endogenous enzymes catalyzed aldehyde reduction in the BT production bioprocess and that YqhD in E. coli was a main ALR for BT production. In addition, ADH2 from Saccharomyces cerevisiae can effectively catalyze 3,4-dihydroxybutanal to BT. Also, YjhG was identified as the major xylonate dehydratase and was co-overexpressed with YqhD, resulting in an improvement of BT production by 30%. Moreover, we identified and eliminated the competing branch pathway by inactivating 2-keto acid reductases (yiaE). Finally, the combination of these approaches led to BT production of 5.1g/L. In summary, our study provides insights into the biosynthetic pathway for BT production, demonstrates an effective strategy to enhance BT production, and paves the way toward in-depth research on BT biosynthesis.
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, PR China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, PR China.
authors.forename: Jinbao
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Life Science, Beijing Institute of Technology, Beijing 100081, PR China. Electronic address: hj_gao@bit.edu.cn.
authors.forename: Haijun
authors.initials: H
authors.lastname: Gao
mesh_terms: D000449:Aldehyde Reductase / Q000235:genetics / Q000378:metabolism; D053898:Biosynthetic Pathways; D000440:Butanols / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D005798:Genes, Bacterial; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism; D007651:Keto Acids / Q000378:metabolism; D060847:Metabolic Engineering / Q000379:methods; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014994:Xylose / Q000378:metabolism*
chemical_list: C000610906:1,2,4-butanetriol; D000440:Butanols; D029968:Escherichia coli Proteins; D007651:Keto Acids; D011994:Recombinant Proteins; D014994:Xylose; D010088:Oxidoreductases; D000449:Aldehyde Reductase; C528732:YqhD protein, E coli; D006836:Hydro-Lyases
keywords: 1,2,4-Butanetriol; aldehyde reductase; branch pathway; metabolic pathway; xylonate dehydratase