Two Biosynthetic Pathways in Jahnella thaxteri for Thaxteramides, Distinct Types of Lipopeptides

The structures of five linear lipopeptides, thaxteramides A1, A2, B1, B2, and C isolated from the myxobacterium Jahnella thaxteri, were elucidated. They have a C-terminal common tetrapeptidic Tyr-Gly-β-Ala-Tyr core but differ in the stereochemistry of the tyrosine units, methylations, the remaining amino acids, and the N-terminal polyketide. In silico analysis of the genome sequence complemented with feeding experiments revealed two distinct hybrid PKS/NRPS gene clusters. Three semisynthesized cyclic analogues were found to inhibit the growth of Gram-positive bacteria.