New lactimidomycin congeners shed insight into lactimidomycin biosynthesis in Streptomyces amphibiosporus
New lactimidomycin congeners shed insight into lactimidomycin biosynthesis in Streptomyces amphibiosporus
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DOI：
10.1021/ol702249g
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发表时间：
2007-12-06
期刊：
影响因子：
5.2
通讯作者：
Shen, Ben
中科院分区：
文献类型：
--
作者：
Ju, Jianhua;Seo, Hong-Woo;Shen, Ben
拉克米霉素(Lactimidmycin，LTM，1)是一种来自两栖孢子链霉菌ATCC53964的具有戊二酰亚胺侧链的大环内酯类抗肿瘤抗生素，为了进一步开发LTM及其类似物作为候选药物，我们(1)将LTM的产量提高了近20倍，(Ii)鉴定了三种可能参与LTM生物合成途径的新代谢物(2-4)；(Iii)发现了3种与先前确定的异孕酮前体相同的代谢物；(Iv)确定了LTM的绝对立体化学，以及(V)产生了新的LTM重排产物2a-d和4a-d。
Lactimidomycin (LTM, 1) is a macrolide antitumor antibiotic with a glutarimide side chain from Streptomyces amphibiosporus ATCC53964, To further develop LTM and related analogues as drug candidates we have (1) improved LTM production by similar to 20 fold, (ii) identified three new metabolites (2-4) possibly involved in the LTM biosynthetic pathway; (iii) found 3 to be identical with a previously identified isomigrastatin precursor, (iv) determined the absolute stereochemistry of LTM, and (v) produced new LTM rearrangement products 2a-d and 4a-d.