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Xiaodong Liu, Zheng Cui and Steven G Van Lanen
University of Kentucky, USA
Posters & Accepted Abstracts: Organic Chem Curr Res
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. Structurally different from other nucleoside antibiotics such as A-90289, caprazamycin, and muraymycin, the nucleoside moiety of albomycin has two features: 1) the stereo configuration of 5ΓΆΒ?Β?-C-glycyluridine (GlyU) in albomycin is (5ΓΆΒ?Β?R, 6ΓΆΒ?Β?S), which is different from (5ΓΆΒ?Β?S, 6ΓΆΒ?Β?S) in the other nucleoside antibiotics and 2) A sulfur atom replaced 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-5ΓΆΒ?Β?-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 covalent bonded a pyridoxal- 5ΓΆΒ?Β?-phosphate as cofactor. AbmH 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 (5ΓΆΒ?Β?R, 6ΓΆΒ?Β?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.
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