Discovery of Paenibacillaceae Family Gram-Negative-Active Cationic Lipopeptide Antibiotics Using Evolution-Guided Chemical Synthesis

Org Lett. 2022 Jul 15;24(27):4943-4948. doi: 10.1021/acs.orglett.2c01879. Epub 2022 Jul 1.

Abstract

Cationic nonribosomal lipopeptides (CNRLPs) from Paenibacillus spp. have been a rewarding source of Gram-negative-active antibiotics. Here we systematically screened sequenced bacterial genomes for CNRLP biosynthetic gene clusters (BGCs) that we predicted might encode additional Gram-negative-active antibiotics. Total chemical synthesis of the bioinformatically predicted products of seven such BGCs led to our identification of new laterocidine, tridecaptin, and paenibacterin-like antibiotics with potent activity against both multiple-drug-resistant Gram-negative and Gram-positive pathogens.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Genome, Bacterial
  • Lipopeptides / pharmacology
  • Multigene Family
  • Paenibacillus* / genetics

Substances

  • Anti-Bacterial Agents
  • Lipopeptides