Reductive Release from a Hybrid PKS‐NRPS during the Biosynthesis of Pyrichalasin H

Abstract: Three central steps during the biosynthesis of cytochalasan precursors, including reductive release, Knoevenagel cyclisation and Diels Alder cyclisation are not yet understood at a detailed molecular level. In this work we investigated the reductive release step catalysed by a hybrid polyketide synthase non‐ribosomal peptide synthetase (PKS‐NRPS) from the pyrichalasin H pathway. Synthetic thiolesters were used as substrate mimics for in vitro studies with the isolated reduction (R) and holo‐thiolation (T) domains of the PKS‐NRPS hybrid PyiS. These assays demonstrate that the PyiS R‐domain mainly catalyses an NADPH‐dependent reductive release of an aldehyde intermediate that quickly undergoes spontaneous Knoevenagel cyclisation. The R‐domain can only process substrates that are covalently bound to the phosphopantetheine thiol of the upstream T‐domain, but it shows little selectivity for the polyketide.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Reductive Release from a Hybrid PKS‐NRPS during the Biosynthesis of Pyrichalasin H ; day:27 ; month:11 ; year:2023 ; extent:9 ; Chemistry - a European journal ; (27.11.2023) (gesamt 9)

Contributors, Places and Time

• Creator: Heinemann, Henrike ; Zhang, Haili ; Cox, Russell

Further information

• DOI: 10.1002/chem.202302590
• URN: urn:nbn:de:101:1-2023112814293363086214
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:29 AM CEST