Abstract:[Background] 2,2'-bipyridines, a class of antimicrobial compounds produced by actinomycetes, have significant antifungal activities and are featured by the 2,2'-bipyridine moiety. No deactivated compound after post-translational modification of the known 2,2'-bipyridines has been discovered, and the self-resistance mechanisms of microorganisms to these compounds remain to be reported. [Objective] To isolate, identify, and determine the antifungal activities of 2,2'-bipyridines from Streptomyces sp. HKIB0006, evaluate the effect of post-translational modification on the antifungal activity, and decipher the self-resistance mechanism of the strain to 2,2'-bipyridines. [Methods] We screened out a Streptomyces strain with anti-fungal activity by the disk diffusion method and then identified the strain by genome sequencing. The target compounds were separated by silica gel column chromatography and HPLC, and their structures were elucidated by MS and nuclear magnetic resonance spectroscopy. The antifungal activities of the isolated compounds were evaluated, and a glycosyltransferase responsible for the self-resistance was revealed by sequence alignment. [Results] Two 2,2'-bipyridines were isolated from the fermentation broth of Streptomyces sp. HKIB0006. One was a new compound named as 11-O-gluconicacid-collismycin A (1), and the other was the known antibiotic collismycin A (2). The antifungal assay of 1 and 2 showed that 1 was inactive and 2 was active. [Conclusion] The antibacterial activity of compounds 1 and 2 was tested. The compound 1 is a gluconic acid modification product of collismycin A, and it is inactive due to the gluconic acid modification. According to genetic analysis, we propose that the gluconic acid modification may represents one of the self-resistance mechanisms of strain HKIB0006 against collismycin A.
