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

Author

Listed:
  • Cláudio J. R. Frazão

    (TU Dresden)

  • Nils Wagner

    (TU Dresden)

  • Kenny Rabe

    (TU Dresden)

  • Thomas Walther

    (TU Dresden)

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.

Suggested Citation

  • Cláudio J. R. Frazão & Nils Wagner & Kenny Rabe & Thomas Walther, 2023. "Construction of a synthetic metabolic pathway for biosynthesis of 2,4-dihydroxybutyric acid from ethylene glycol," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37558-x
    DOI: 10.1038/s41467-023-37558-x
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    References listed on IDEAS

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