Engineering E. coli for the biosynthesis of 3-hydroxy-γ-butyrolactone (3HBL) and 3,4-dihydroxybutyric acid (3,4-DHBA) as value-added chemicals from glucose as a sole carbon source
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Author(s)
Tarasova, Yekaterina
Martin, Collin H.
Dhamankar, Himanshu Hemant
Prather, Kristala L
Date Issued
June 2014
Journal
Metabolic Engineering
Publisher
Elsevier
Citation
Dhamankar, Himanshu, Yekaterina Tarasova, Collin H. Martin, and Kristala L.J. Prather. “Engineering E. Coli for the Biosynthesis of 3-Hydroxy-γ-Butyrolactone (3HBL) and 3,4-Dihydroxybutyric Acid (3,4-DHBA) as Value-Added Chemicals from Glucose as a Sole Carbon Source.” Metabolic Engineering 25 (September 2014): 72–81.
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Author's final manuscript
Abstract
3-hydroxy-γ-butyrolactone (3HBL) is a versatile chiral synthon, deemed a top value-added chemical from biomass by the DOE. We recently reported the first biosynthetic pathway towards 3HBL and its hydrolyzed form, 3,4-dihydroxybutyric acid (3,4-DHBA) in recombinant Escherichia coli using glucose and glycolic acid as feedstocks and briefly described their synthesis solely from glucose. Synthesis from glucose requires integration of the endogenous glyoxylate shunt with the 3,4-DHBA/3HBL pathway and co-overexpression of seven genes, posing challenges with respect to expression, repression of the glyoxylate shunt and optimal carbon distribution between the two pathways. Here we discuss engineering this integration. While appropriate media and over-expression of glyoxylate shunt enzymes helped overcome repression, two orthogonal expression systems were employed to address the expression and carbon distribution challenge. Synthesis of up to 0.3 g/L of 3HBL and 0.7 g/L of 3,4-DHBA solely from glucose was demonstrated, amounting to 24% of the theoretical maximum.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Microbiology Graduate Program
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DOI of Published Version
https://doi.org/10.1016/j.ymben.2014.06.004
