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Development of a New 1,2,4-butanetriol Biosynthesis Pathway in an Engineered Homoserine-producing Strain of Escherichia coli

Synthetic Biology and Engineering. 2023, 1(1), 10007; https://doi.org/10.35534/sbe.2023.10007
Yujun Zhang 1,    Lin Chen 1,    Antu Thomas 1,    An-Ping Zeng 1, 2, *   
1
Hamburg University of Technology, Institute of Bioprocess and Biosystems Engineering, Hamburg, Germany
2
Present Address: Center of Synthetic Biology and Integrated Bioengineering, School of Engineering, Westlake University, Hangzhou, China
*
Authors to whom correspondence should be addressed.

Received: 06 Feb 2023    Accepted: 05 May 2023    Published: 10 May 2023   

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Abstract

1,2,4-butanetriol (BT) is a compound of high interest with applications in pharmaceutical and materials. In this work, we designed a novel biosynthetic pathway for BT from glucose via a nonessential amino acid homoserine. This non-natural pathway used an engineered phosphoserine transaminase (SerCR42W/R77W) to achieve the deamination of homoserine to 4-hydroxy-2-oxobutanoic acid (HOBA). Three consecutive enzymes including a lactate dehydrogenase, a 4-hydroxybutyrate CoA-transferase and a bifunctional aldehyde/alcohol dehydrogenase are used to catalyze HOBA to BT. To enhance the carbon flux to homoserine, a homoserine-producing Escherichia coli was developed by improving the overexpression of two relevant key genes metL and lysC (V339A). The simultaneous overexpression of the genes encoding these enzymes for the homoserine-derived BT pathway enabled production of 19.6 mg/L BT from glucose in the homoserine-producing E. coli.

Keywords

1,2,4-butanetriol; Synthetic pathway; Homoserine; Escherichia coli

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