Precursor-directed biosynthesis: Biochemical basis of the remarkable selectivity of the erythromycin polyketide synthase toward unsaturated triketides
Precursor-directed biosynthesis: Biochemical basis of the remarkable selectivity of the erythromycin polyketide synthase toward unsaturated triketides
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DOI：
10.1016/s1074-5521(02)00089-3
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发表时间：
2002-01-01
影响因子：
--
通讯作者：
Khosla, C
中科院分区：
文献类型：
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作者：
Cane, DE;Kudo, F;Khosla, C
通过将一系列不饱和三酮化合物的N-乙酰基半胱胺（-SNAC）酯与DEBS模块2+TE孵育，研究了三酮化合物类似物之间显著的立体化学区分的结构基础。三酮化合物类似物首先在延伸底物甲基丙二酰-CoA和NADPH存在下在一组标准短期孵育条件下筛选。对于充当模块2+TE的底物的那些三酮化合物类似物，定量由k（cat）/K-M值表示的相对特异性。三酮化合物非对映异构体通过DEBS（KS 1degrees）转化为不饱和的16元环大环内酯类化合物，是DEBS模块2+TE的良好至优异的底物，而类似物通过DEBS（KS 1degrees）转化为10，11-双氧-6-脱氧双氧萘烷B的14元环类似物，则完全不被模块2+TE转化。
The structural basis for the striking stereochemical discrimination among triketide analogs has been investigated by incubating a series of N-acetyl cysteamine (-SNAC) esters of unsaturated triketides with DEBS module 2+TE. The triketide analogs were first screened under a standard set of short-term incubation conditions in the presence of the extender substrate methylmalonyl-CoA and NADPH. For those triketide analogs that served as substrates for module 2+TE, the relative specificity, represented by the k(cat)/K-M values, was quantitated. Triketide diastereomers that were converted in precursor-directed biosynthesis experiments to unsaturated 16-membered rings macrolides by DEBS(KS1degrees) were good to excellent substrates for DEBS module 2+TE, whereas analogs that were converted to the 14-membered ring analogs of 10,11-dehydro-6-deoxyerythronolide B by DEBS(KS1degrees) were not turned over at all by module 2+TE.