Genome- and Mass Spectrometry-Guided Discovery of Ralstoamides A and B from Ralstonia solanacearum Species Complex

• Published in: ACS chemical biology 2020-11, Vol.15 (11), p.2860-2865
• Main Authors: Komatsu, Shoko, Tsumori, Chiaki, Ohnishi, Kouhei, Kai, Kenji
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - genetics; Genome, Bacterial; Lipopeptides - chemistry; Lipopeptides - genetics; Mass Spectrometry; Nicotiana - microbiology; Peptide Synthases - genetics; Polyketide Synthases - genetics; Ralstonia solanacearum - chemistry; Ralstonia solanacearum - genetics; Solanum lycopersicum - microbiology
• ISSN: 1554-8929; 1554-8937
• DOI: 10.1021/acschembio.0c00605

Strains of Ralstonia solanacearum species complex (RSSC) are devastating plant pathogens distributed globally with a wide host range and genetic diversity. Many RSSC strains harbor the polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrid gene rmyA/rmyB for ralstonin production. We report that ralstoamides A (1) and B (2), which are ralstonin-like but shorter lipopeptides, were discovered from the Japanese strains using accumulated RSSC genome data and LC/MS-based metabolite analysis. Their structures, including absolute configurations, were elucidated by spectroscopic analysis and chemical techniques. ramA, a PKS-NRPS gene for ralstoamide production, was identified from the producer strains by genome sequencing and gene-deletion experiments. Based on the analysis of biosynthetic genes of ralstoamides and ralstonins, we suggest the occurrence of NRPS-module reduction of rmyA/rmyB genes in some RSSC strains. This possible molecular evolution changed not only the structures, but also the biological activity of RSSC lipopeptides.