Intrinsic Ability of the β‐Oxidation Pathway To Produce Bioactive Styrylpyrones. (13th July 2022)

• Record Type: Journal Article
• Authors: Huang, Ying; Hoefgen, Sandra; Gherlone, Fabio; Valiante, Vito
• Is Part Of: Angewandte Chemie. Volume 134:Number 34(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-07-13
• Subjects: α-Pyrones -- β-Oxidation -- Polyketides -- Styrylpyrones -- Thiolases; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202206851
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: 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 styrylpyrones in other species, demonstrating that the intrinsic ability of the β‐oxidation pathway allows for the synthesis of such molecules in bacteria, revealing an important biological feature hitherto neglected. Abstract : The fatty acid β‐oxidation‐related ligase FadD and thiolases FadA/FadI in E. coli can utilise phenylpropionic acid derivatives as starting substrates for the biosynthesis of styrylpyrones through iterative non‐decarboxylative Claisen condensation steps. Targeted feeding experiments led to the detection of styrylpyrones in other species, suggesting that the ubiquitous β‐oxidation pathway enables the synthesis of such molecules in bacteria.