biostudies-literatureHuang YDeutsche Forschungsgemeinschafte202206851https://www.ebi.ac.uk/biostudies/studies/S-EPMC9541201biostudies-literatureUnknown61(34)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 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 styrylpyroneAngewandte Chemie (International ed. in English)Intrinsic Ability of the β-Oxidation Pathway To Produce Bioactive Styrylpyrones.PMC9541201453246485390713860Huang YHoefgen SGherlone FValiante VfalseIntrinsic 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 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 styrylpyrone2022-01-01T00:00:00Z2022 Aug2025-04-22T02:01:39.038Z2025-04-05T20:11:59.469ZS-EPMC95412013572667210.1002/anie.202206851