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Pikromycin : ウィキペディア英語版
Pikromycin

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Pikromycin was studied by Brokmann and Hekel in 1951 and was the first antibiotic macrolide to be isolated.
Pikromycin is synthesized through a type I polyketide synthase system in ''Streptomyces venezuelae'', a species of Gram-positive bacterium in the ''Streptomyces'' genus.
Pikromycin is derived from narbonolide, a 14-membered ring macrolide.

Along with the narbonolide backbone, pikromycin includes a desosamine sugar and a hydroxyl group. Although Pikromycin is not a clinically useful antibiotic, it can be used as a raw material to synthesize antibiotic ketolide compounds such as ertythromycins and new epothilones.

==Biosynthesis ==

The pikromycin polyketide synthase of ''Streptomyces venezuelae'' contains four polypeptides: PikAI, PikAII, PikAIII, and PikAIV. These polypeptides contain a loading module, six extension molecules, and a thioesterase domain that that terminated the biosynthetic procedure.

Recently electron cryo-microscopy have been used to determine sub-nanometre-resolution three- dimensional reconstructions of a full-length PKS module from the bacterium Streptomyces venezuelae that revealed an unexpectedly different architecture.

In Figure 1, each circle corresponds to a PKS mutilifuctional protein, where ACP is acyl carrier protein, KS is keto-ACP synthase, KSQ is a keto-ACP synthase like domain, AT is acyltransferase, KR is keto ACP reductase, KR with cross is inactive KR, DH is hydroxyl-thioester dehydratase, ER is enoyl reductase, TEI is thioesterase domain I, TEII is type II thioesterase.

Des corresponds to the enzymes utilized in desosamine biosynthesis and transfer, which include DesI-DesVIII.
Figure 2 represents the desosamine deoxyamino sugar biosynthetic pathway. DesI-DesVI (des locus of pikromycin PKS) encodes all the enzymes needed to obtain TDP-desoamine from TDP-glucose. DesVII and DesVIII activities transfer desoamine to narbonolide and narbomycin is obtained. PikC cytochrome P450 hydrolase catalyzes the hydroxylation of narbomycin to obtain pikromycin.



抄文引用元・出典: フリー百科事典『 ウィキペディア(Wikipedia)
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