Construction of a synthetic metabolic pathway for biosynthesis of 2,4-dihydroxybutyric acid from ethylene glycol

Cláudio J. R. Frazão, Nils Wagner, Kenny Rabe and Thomas Walther ()
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Cláudio J. R. Frazão: TU Dresden
Nils Wagner: TU Dresden
Kenny Rabe: TU Dresden
Thomas Walther: TU Dresden

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract Ethylene glycol is an attractive two-carbon alcohol substrate for biochemical product synthesis as it can be derived from CO2 or syngas at no sacrifice to human food stocks. Here, we disclose a five-step synthetic metabolic pathway enabling the carbon-conserving biosynthesis of the versatile platform molecule 2,4-dihydroxybutyric acid (DHB) from this compound. The linear pathway chains ethylene glycol dehydrogenase, D-threose aldolase, D-threose dehydrogenase, D-threono-1,4-lactonase, D-threonate dehydratase and 2-oxo-4-hydroxybutyrate reductase enzyme activities in succession. We screen candidate enzymes with D-threose dehydrogenase and D-threonate dehydratase activities on cognate substrates with conserved carbon-centre stereochemistry. Lastly, we show the functionality of the pathway by its expression in an Escherichia coli strain and production of 1 g L−1 and 0.8 g L−1 DHB from, respectively, glycolaldehyde or ethylene glycol.

Date: 2023
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DOI: 10.1038/s41467-023-37558-x

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