Towards an enzyme cascade synthesis of the bulk chemical acrylic acid.
basic_science · Level V
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- Record sourced from PubMed, PMID 42477336.
- Also identified by DOI 10.1038/s41467-026-75484-w.
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Abstract
Acrylic acid is a bulk chemical predominantly produced via fossil-based processes. Here, we repurpose and engineer a thiamine diphosphate (ThDP)-dependent enzyme to catalyze direct <math xmlns="http://www.w3.org/1998/Math/MathML"><msub><mrow><mi>H</mi></mrow><mrow><mn>2</mn></mrow></msub><msubsup><mrow><mi>PO</mi></mrow><mrow><mn>4</mn></mrow><mrow><mo>-</mo></mrow></msubsup></math> elimination from dihydroxyacetone phosphate (DHAP) for acrylic acid synthesis. Quantum chemical calculations reveal the catalytic mechanism involving isomerization, enol-ThDP intermediate formation, <math xmlns="http://www.w3.org/1998/Math/MathML"><msub><mrow><mi>H</mi></mrow><mrow><mn>2</mn></mrow></msub><msubsup><mrow><mi>PO</mi></mrow><mrow><mn>4</mn></mrow><mrow><mo>-</mo></mrow></msubsup></math> elimination, and hydrolysis. Using an automated high-throughput screening platform, we perform directed evolution and obtain a 13.6-fold improved variant, designated acrylic acid synthase (AAS). We establish an enzymatic methanol-to-acrylic acid (MAAP) pathway, achieving a titer of 4.3 g L<sup>-1</sup>, a productivity of 268.9 mg L<sup>-1</sup> h<sup>-1</sup>, and 99.5% conversion. This work establishes a high-efficiency biomanufacturing paradigm for bulk acrylic acid, and expands the catalytic repertoire of ThDP-dependent enzymes for sustainable one-carbon conversion.