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

Naturally occurring alpha-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 beta-oxidation pathway in Escherichia coli, namely the CoA ligase FadD and the thiolases FadA and FadI, can synthesise styrylpyrones with phenylpropionic acids in vivo. The two thiolases directly utilise acetyl-CoA as an extender unit for carbon-chain elongation through a non-decarboxylative Claisen condensation, thus making the overall reaction more efficient in terms of carbon and energy consumption. Moreover, using a cell-free approach, different styrylpyrones were synthesised in vitro. Finally, targeted feeding experiments led to the detection of styrylpyrones in other species, demonstrating that the intrinsic ability of the beta-oxidation pathway allows for the synthesis of such molecules in bacteria, revealing an important biological feature hitherto neglected.

Automated summary

Enzymes in Escherichia coli can synthesize styrylpyrones with phenylpropionic acids through a non-decarboxylative Claisen condensation, making the reaction more efficient. Different styrylpyrones can also be synthesized in vitro using a cell-free approach. Targeted feeding experiments demonstrate the ability to synthesize these molecules in bacteria.