Structure elucidation of the syringafactin lipopeptides provides insight in the evolution of nonribosomal peptide synthetases.

Götze S, Arp J, Lackner G, Zhang S, Kries H, Klapper M, García-Altares M, Willing K, Günther M, Stallforth P (2019) Structure elucidation of the syringafactin lipopeptides provides insight in the evolution of nonribosomal peptide synthetases. Chem Sci 10(48), 10979-10990.

Abstract

Modular biosynthetic machineries such as polyketide synthases (PKSs) or nonribosomal peptide synthetases (NRPSs) give rise to a vast structural diversity of bioactive metabolites indispensable in the treatment of cancer or infectious diseases. Here, we provide evidence for different evolutionary processes leading to the diversification of modular NRPSs and thus, their respective products. Discovery of a novel lipo-octapeptide family from Pseudomonas, the virginiafactins, and detailed structure elucidation of closely related peptides, the cichofactins and syringafactins, allowed retracing recombinational diversification of the respective NRPS genes. Bioinformatics analyses allowed us to spot an evolutionary snapshot of these processes, where recombination occurred both within the same and between different biosynthetic gene clusters. Our systems feature a recent diversification process, which may represent a typical paradigm to variations in modular biosynthetic machineries.

Leibniz-HKI-Authors

Johannes Arp
María García-Altares Pérez
Sebastian Götze
Markus Günther
Martin Klapper
Hajo Kries
Gerald Lackner
Pierre Stallforth
Karsten Willing
Shuaibing Zhang

Identifier

doi: 10.1039/c9sc03633d

PMID: 32953002