Genome mining and heterologous expression reveal streptacidin, a new lasso peptide from .

A lasso peptide biosynthetic gene cluster (BGC) was identified through genome mining in the species CGMCC 4.1857, which was isolated from acidic rhizosphere soil. The BGC was reconstructed in , leading to the heterologous production of a lasso peptide named streptacidin. The solution structure of streptacidin was determined based on the distance constraints derived from the NOESY spectrum, establishing the first lasso peptide utilizing methionine as a steric lock for the unique spatial configuration and the remarkable stability against heat (up to 95 °C) and proteolytic degradation by carboxypeptidase Y and chymotrypsin. Under experimental conditions, streptacidin showed weak effectiveness against vancomycin sensitive ATCC 29212 and ATCC 902. These findings further the understanding of this distinctive class of compounds.