Journal of Bacteriology & Parasitology

Elucidate the biosynthesis of nucleoside moiety in albomycin

5^th International Congress on Bacteriology and Infectious Diseases

May 25-26, 2017 Chicago, USA

Xiaodong Liu, Zheng Cui and Steven G Van Lanen

University of Kentucky, USA

Posters & Accepted Abstracts: J Bacteriol Parasitol

Abstract:

Albomycins are broad-spectrum antibiotics isolated from soil-dwelling actinomycetes. The albomycins have a minimum inhibitory concentration (MIC) as low as 10 ng/mL against Streptococcus pneumonia. Studies revealed that albomycins are Trojan horse antibiotics that consist of a siderphore component that is indiscriminately taken up by bacteria as an iron source. Once inside the cell, the albomycins are hydrolyzed to release a nucleoside compound SB-217452, which works as an enzyme inhibitor of bacterial seryl-tRNA synthetase, which is structurally different from other nucleoside antibiotics such as A-90289, caprazamycin and muraymycin. The nucleoside moiety of albomycin has two features: The stereo configuration of 5�??-C-glycyluridine (GlyU) in albomycin is (5�??R, 6�??S), which is different from (5�??S, 6�??S) in the other nucleoside antibiotics; a sulfur atom replacing the oxygen atom on the pentose ring in albomycin. Gene cluster analyzing indicated that AbmH, a homologue of LipK, is responsible for the incorporation of glycine moiety to the uridine aldehyde. LipK was functionally characterized as a L-threonine: Uridine-5�??-aldehyde transaldolase, which catalyzes the C-C bond-forming during the biosynthesis of the GlyU in A-90289. Further characterization of AbmH in vitro found that it is covalently bonded to a pyridoxal-5�??-phosphate as a cofactor. AbmH has catalyzed an aldo-type reaction to incorporate the glycine moiety on L-threonine to uridine aldehyde to form the GlyU. The product GlyU was confirmed to have (5�??R, 6�??S) stereo configuration, same as the structure in albomycin. Different substrates test showed that L-allo-threonine could also be used as a substrate in reaction.

Biography :

Email: liuxd03@gmail.com