Chaxapeptin, a Lasso Peptide from Extremotolerant Streptomyces leeuwenhoekii Strain C58 from the Hyperarid Atacama Desert

• Published in: Journal of organic chemistry Vol. 80; no. 20; pp. 10252 - 10260
• Main Authors: Elsayed, Somayah S, Trusch, Franziska, Deng, Hai, Raab, Andrea, Prokes, Ivan, Busarakam, Kanungnid, Asenjo, Juan A, Andrews, Barbara A, van West, Pieter, Bull, Alan T, Goodfellow, Michael, Yi, Yu, Ebel, Rainer, Jaspars, Marcel, Rateb, Mostafa E
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 16.10.2015; Amer Chemical Soc
• Subjects: Amino Acid Sequence; Biological Products - chemistry; Cell Line - chemistry; Chemistry; Chemistry, Organic; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - metabolism; Macrolides - chemistry; Macrolides - pharmacology; Magnetic Resonance Spectroscopy; Peptides - chemical synthesis; Peptides - chemistry; Peptides, Cyclic - chemical synthesis; Peptides, Cyclic - chemistry; Peptides, Cyclic - pharmacology; Physical Sciences; Ribosomes - chemistry; Science & Technology; Streptomyces - chemistry; GENE-CLUSTER; NATURAL-PRODUCT DISCOVERY; BIOSYNTHESIS; CHAXAMYCINS; A-D; MICROBIOLOGY; HETEROLOGOUS EXPRESSION; CHILE; MASS-SPECTROMETRY; INSIGHTS
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.5b01878

Lasso peptides are ribosomally synthesized and post-translationally modified peptides (RiPPs) that possess a unique “lariat knot” structural motif. Genome mining-targeted discovery of new natural products from microbes obtained from extreme environments has led to the identification of a gene cluster directing the biosynthesis of a new lasso peptide, designated as chaxapeptin 1, in the genome of Streptomyces leeuwenhoekii strain C58 isolated from the Atacama Desert. Subsequently, 1 was isolated and characterized using high-resolution electrospray ionization mass spectrometry and nuclear magnetic resonance methods. The lasso nature of 1 was confirmed by calculating its nuclear Overhauser effect restraint-based solution structure. Chaxapeptin 1 displayed a significant inhibitory activity in a cell invasion assay with human lung cancer cell line A549.