Absolute Configuration and Antibiotic Activity of Piceamycin

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2020-02, Vol.83 (2), p.277-285
• Main Authors: Shin, Yern-Hyerk, Kang, Saeyeon, Byun, Woong Sub, Jeon, Chang-Wook, Chung, Beomkoo, Beom, Ji Yoon, Hong, Suckchang, Lee, Jeeyeon, Shin, Jongheon, Kwak, Youn-Sig, Lee, Sang Kook, Oh, Ki-Bong, Yoon, Yeo Joon, Oh, Dong-Chan
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Biological Products - chemistry; Biological Products - metabolism; Biosynthetic Pathways; Humans; Lactams, Macrocyclic - chemistry; Microbial Sensitivity Tests; Molecular Structure; Proteus - chemistry; Stereoisomerism; Streptomyces - chemistry
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.9b00678

The cultivation of a Streptomyces sp. SD53 strain isolated from the gut of the silkworm Bombyx mori produced two macrolactam natural products, piceamycin (1) and bombyxamycin C (2). The planar structures of 1 and 2 were identified by a combination of NMR, MS, and UV spectroscopic analyses. The absolute configurations were assigned based on chemical and chromatographic methods as well as ECD calculations. A new chromatography-based experimental method for determining the configurations of stereogenic centers β to nitrogen atoms in macrolactams was established and successfully applied in this report. These compounds exhibited significant bioactivities against the silkworm entomopathogen Bacillus thuringiensis and various human pathogens as well as human cancer cell lines. In particular, piceamycin potently inhibited Salmonella enterica and Proteus hauseri with MIC values of 0.083 μg/mL and 0.025 μg/mL, respectively. The biosynthetic pathway involved in the formation of the cyclopentenone moiety in piceamycin is discussed.