Heterologous Expression of a lasso peptide from Rothia aeria from the human lung microbiome

The functions of ribosomally synthesized and post-translationally modified peptides (RiPPs) have already been studied in detail in various contexts of the human microbiota, as they represent a widely distributed class of natural products in bacteria (Arnison et al. 2013; Barbour et al. 2022; Benjdia und Berteau 2021; Bushin et al. 2020; Clark et al. 2022; Li und Rebuffat 2020; McIntosh et al. 2009). These peptides are known for their antimicrobial properties in competitive and regulatory processes in the microbiome (Barbour et al. 2022; Li und Rebuffat 2020). Some members of the lasso peptide subgroup, which are marked by their intriguing spatial structure and resulting chemical properties, have already been identified as antibiotic peptides (Bayro et al. 2003; Salomón und Farías 1992; Tan et al. 2019). In this context, we are investigating a gene cluster encoding a lassopeptide found in Rothia aeria, an organism of the oral and respiratory microbiome (Sonehara et al. 2021; Tsuzukibashi et al. 2017). The corresponding natural product was produced by heterologous expression in E. coli and in two different Streptomyces species and then comprehensively characterized. Particular attention was paid to its role in the lung microbiome, which was investigated in detail in a previously established microbiome model.