Identification of the Biosynthetic Gene Cluster of New Piperazic Acid-Containing Lipopeptides with Cytotoxic Activity in the Genome of Marine Streptomyces PHM034

Three novel lipopeptides, PM130391 (1), PM130392 (2), and PM140293 (3) were obtained from cultures of <i>Streptomyces tuirus</i> PHM034 isolated from a marine sediment. Structural elucidation of the three compounds showed they belong to the nonribosomal peptides family, and they all cont...

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Bibliographic Details
Main Authors: Ana Ceniceros, Librada Cañedo, Carmen Méndez, Carlos Olano, Carmen Schleissner, Carmen Cuevas, Fernando de la Calle, José A. Salas
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Metabolites
Subjects:
Online Access:https://www.mdpi.com/2218-1989/13/10/1091
Description
Summary:Three novel lipopeptides, PM130391 (1), PM130392 (2), and PM140293 (3) were obtained from cultures of <i>Streptomyces tuirus</i> PHM034 isolated from a marine sediment. Structural elucidation of the three compounds showed they belong to the nonribosomal peptides family, and they all contain an acylated alanine, three piperazic acids, a methylated glycine, and an N-hydroxylated alanine. The difference between the three compounds resides in the acyl chain bound to the alanine residue. All three compounds showed cytotoxic activity against human cancer cell lines. Genome sequence and bioinformatics analysis allowed the identification of the gene cluster responsible for the biosynthesis. Inactivation of a nonribosomal peptide synthase of this cluster abolished the biosynthesis of the three compounds, thus demonstrating the involvement of this cluster in the biosynthesis of these lipopeptides.
ISSN:2218-1989