Journal
METABOLIC ENGINEERING
Volume 41, Issue -, Pages 39-45Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymben.2017.03.003
Keywords
3-hydroxy-gamma-butyrolactone; 3; 4-dihydroxybutyric acid; Xylose metabolism; Metabolic engineering; Escherichia coli
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Funding
- College of Engineering, The University of Georgia, Athens
- National Natural Science Foundation of China [21406010, 21376017, 21636001]
- Changjiang Scholars and Innovative Research Team in Universities in China [IRT13045]
- Programme of Introducing Talents of Discipline (111 project) [B13005]
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3-Hydroxy-gamma-butyrolactone (3HBL) is an attractive building block owing to its broad applications in pharmaceutical industry. Currently, 3HBL is commercially produced by chemical routes using petro-derived carbohydrates, which involves hazardous materials and harsh processing conditions. Only one biosynthetic pathway has been reported for synthesis of 3HBL and its hydrolyzed form 3,4-dihydroxybutyric acid (3,4-DHBA) using glucose and glycolic acid as the substrates and coenzyme A as the activator, which involves multiple steps (> 10 steps) and suffers from low productivity and yield. Here we established a novel five-step biosynthetic pathway for 3,4-DHBA generation from D-xylose based on the non-phosphorylative D-xylose metabolism, which led to efficient production of 3,4-DHBA in Escherichia coli. Pathway optimization by incorporation of efficient enzymes for each step and host strain engineering by knocking out competing pathways enabled 1.27 g/L 3,4-DHBA produced in shake flasks, which is the highest titer reported so far. The novel pathway established in engineered E. coli strain demonstrates a new route for 3,4-DHBA biosynthesis from xylose, and this engineered pathway has great potential for industrial biomanufacturing of 3,4-DHBA and 3HBL.
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