Total and chemoenzymatic synthesis of the lipodepsipeptide rhizomide A

Corinne A Lepetit; André R Paquette; Jordan T Brazeau-Henrie; Christopher N Boddy

doi:10.1016/j.bmcl.2023.129506

Total and chemoenzymatic synthesis of the lipodepsipeptide rhizomide A

Bioorg Med Chem Lett. 2023 Nov 15:96:129506. doi: 10.1016/j.bmcl.2023.129506. Epub 2023 Oct 12.

Authors

Corinne A Lepetit¹, André R Paquette², Jordan T Brazeau-Henrie², Christopher N Boddy³

Affiliations

¹ Department of Chemistry and Biomolecular Sciences, Centre for Chemical and Synthetic Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada; Cergy Paris Université, 5 Mail Gay Lussac, 95000 Cergy, France.
² Department of Chemistry and Biomolecular Sciences, Centre for Chemical and Synthetic Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada.
³ Department of Chemistry and Biomolecular Sciences, Centre for Chemical and Synthetic Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada. Electronic address: cboddy@uottawa.ca.

PMID: 37820774
DOI: 10.1016/j.bmcl.2023.129506

Abstract

Rhizomides are a family of depsipeptide macrolactones synthesized by a non-ribosomal peptide synthetase (NRPS) encoded in the genome of Paraburkholderia rhizoxinica str. HKI 454. In this study, the total and chemoenzymatic synthesis of the depsipeptide rhizomide A is described. Rhizomide A was generated through macrolactamization while thelinear C-terminal N-acetylcysteamine (SNAC) thioester substrate was synthesized through a C-terminal thioesterification strategy. It was shown that the rhizomide A thioesterase (RzmA-TE) is an active macrocyclization catalyst, allowing the chemoenzymatic synthesis of rhizomide A.This work further showcases the biocatalytic power of TEs in accessing complex macrocyclic natural products.

Keywords: Biocatalysis; Chemoenzymatic synthesis; Depsipeptide; Enzymatic assays; Peptide chemistry; Total synthesis.

MeSH terms

Biocatalysis
Catalysis
Cyclization
Depsipeptides*

Substances

Depsipeptides