Microbial synthesis of branched-chain β,γ-diols from amino acid metabolism

Peiling Wu, Haofeng Chen, Yueyang Chen, Yang Zhang and Jifeng Yuan ()
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Peiling Wu: Xiamen University
Haofeng Chen: Xiamen University
Yueyang Chen: Xiamen University
Yang Zhang: Xiamen University
Jifeng Yuan: Xiamen University

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract Microbial synthesis of chemicals using renewable feedstocks has gained interest due to its sustainability. The class of β,γ-diols has unique chemical and physical properties, making them valuable for diverse applications. Here, we report a biosynthetic platform in Escherichia coli for the synthesis of branched-chain β,γ-diols from renewable feedstocks. Firstly, we identify an acetohydroxyacid synthase from Saccharomyces cerevisiae to catalyze the condensation of branched-chain aldehydes with pyruvate, forming α-hydroxyketones. Next, de novo production of branched-chain β,γ-diols (4-methylpentane-2,3-diol, 5-methylhexane-2,3-diol and 4-methylhexane-2,3-diol) is realized from branched-chain amino acids (BCAA) metabolism. After systematic optimization of the BCAA pathway, we have achieved high-specificity production of 4-methylpentane-2,3-diol from glucose, achieving 129.8 mM (15.3 g/L) 4-methylpentane-2,3-diol with 72% of the theoretical yield. In summary, our work demonstrates the synthesis of structurally diverse branched-chain β,γ-diols, highlighting its potential as a versatile carbon elongation system for other β,γ-diol productions.

Date: 2025
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DOI: 10.1038/s41467-025-59753-8

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