Phosphonoalamides Reveal the Biosynthetic Origin of Phosphonoalanine Natural Products and a Convergent Pathway for Their Diversification.

ABSTRACT: Phosphonate natural products, with their potent inhibitory activity, have found widespread use across multiple industries. Their success has inspired development of genome mining approaches that continue to reveal previously unknown bioactive scaffolds and biosynthetic insights. However, a greater understanding of phosphonate metabolism is required to enable prediction of compounds and their bioactivities from sequence information alone. Here, we expand our knowledge of this natural product class by reporting the complete biosynthesis of the phosphonoalamides, antimicrobial tripeptides with a conserved N-terminal l-phosphonoalanine (PnAla) residue produced by Streptomyces. The phosphonoalamides result from the convergence of PnAla biosynthesis and peptide ligation pathways. We elucidate th

SUBMITTER: Cui JJ 

PROVIDER: S-EPMC11867202 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature