Heterologous biosynthesis of the sterol O-acyltransferase inhibitor helvamide unveils an α-ketoglutarate-dependent cross-linking oxygenase

Rui Wang, Jia Jing Liang, Wencong Yang, Daniel Vuong, John A. Kalaitzis, Alastair E. Lacey, Ernest Lacey, Andrew M. Piggott, Yit Heng Chooi*, Hang Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

We have identified the biosynthetic gene cluster (hvm) for the sterol O-acyltransferase inhibitor helvamide (1) from the genome of Aspergillus rugulosus MST-FP2007. Heterologous expression of hvm in A. nidulans produced a previously unreported analog helvamide B (5). An α-ketoglutarate-dependent oxygenase Hvm1 was shown to catalyze intramolecular cyclization of 1 to yield 5. The biosynthetic branch to the related hancockiamides and helvamides was found to be controlled by the substrate selectivity of monomodular nonribosomal peptide synthetases.

Original languageEnglish
Pages (from-to)1807-1812
Number of pages6
JournalOrganic Letters
Volume26
Issue number9
Early online date23 Feb 2024
DOIs
Publication statusPublished - 8 Mar 2024

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