Naturally occurring α-pyrones with biological activities are mostly synthesised by polyketide synthases (PKSs) via iterative decarboxylative Claisen condensations. Remarkably, we found that some enzymes related to the fatty acid ß-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 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 ß-oxidation pathway allows for the synthesis of such molecules in bacteria, revealing an important biological feature hitherto neglected.