Biosynthesis of Largimycins in Streptomyces argillaceus Involves Transient β-Alkylation and Cryptic Halogenation Steps Unprecedented in the Leinamycin Family.

ABSTRACT: Largimycins A1 and A2 are key members of a recently identified family of hybrid nonribosomal peptide polyketides belonging to the scarcely represented group of antitumor leinamycins. They are encoded by the gene cluster lrg of Streptomyces argillaceus. This cluster contains a halogenase gene and two sets of genes for the biosynthesis and incorporation of β branches at C3 and C9. Noticeably, largimycins A1 and A2 are nonhalogenated compounds and only contain a β branch at C3. By generating mutants in those genes and characterizing chemically their accumulated compounds, we could confirm the existence of a chlorination step at C19, the introduction of an acetyl-derived olefinic exomethylene group at C9, and a propionyl-derived β branch at C3 in the biosynthesis pathway. Since t

SUBMITTER: Becerril A 

PROVIDER: S-EPMC9396626 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature