Construction of a synthetic metabolic pathway for biosynthesis of 2,4-dihydroxybutyric acid from ethylene glycol.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 37024485.
- Also identified by DOI 10.1038/s41467-023-37558-x and PMC identifier 10079672.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Ethylene glycol is an attractive two-carbon alcohol substrate for biochemical product synthesis as it can be derived from CO<sub>2</sub> 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<sup>-1</sup> and 0.8 g L<sup>-1</sup> DHB from, respectively, glycolaldehyde or ethylene glycol.
Medical subject headings
- Ethylene Glycol
- Metabolic Engineering