Intrinsic Ability of the β‐Oxidation Pathway To Produce Bioactive Styrylpyrones

Naturally occurring α-pyrones with biological activities are mostly synthesised by polyketide synthases (PKSs) via iterative decarboxylative Claisen condensation steps. Remarkably, we found that some enzymes related to the fatty acid β-oxidation pathway in Escherichia coli, namely CoA ligase FadD and thiolases FadA FadI, can synthesise styrylpyrones phenylpropionic acids vivo. The two directly utilise acetyl-CoA as an extender unit for carbon-chain elongation through a non-decarboxylative condensation, thus making overall reaction more efficient terms of carbon energy consumption. Moreover, using cell-free approach, different were vitro. Finally, targeted feeding experiments led detection other species, demonstrating intrinsic ability allows synthesis such molecules bacteria, revealing important feature hitherto neglected.