Biosynthesis of the pulvomycin aglycon in Streptoverticillium netropis
Biosynthesis of the pulvomycin aglycon in Streptoverticillium netropis
复制标题
内托链轮丝菌中普伏霉素苷元的生物合成
DOI：
10.1021/jo00120a051
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发表时间：
1995
影响因子：
3.6
通讯作者：
S. Groeger
中科院分区：
文献类型：
--
作者：
N. Priestley;S. Groeger
Pulvomycin，1，是一种22元大环聚酮化合物天然产物，可从Streptoveticillium netropis的发酵培养液中分离得到。1957年首次报道了普沃霉素的结构。1963年分离出一种类似的分离物，由于其不稳定性而命名为labilomycin，2 3但随后证明与普沃霉素相同。[4]最初提出的1的结构被接受了近20年，直到注意到1的NMR光谱与其建议的结构之间的不一致。[5] Smith及其同事使用一系列NMR和MS实验确定了1的准确结构。这种抗生素因其作用方式而引起人们的兴趣。像大多数大环内酯类1抑制原核蛋白质合成。1是不寻常的，但是，因为它通过阻断原核延伸因子Tu，GTP和aminoacyPRNA之间的三元复合物的形成而起作用。6仔细观察，1的结构似乎偏离了经典的聚酮生物合成模型。有趣的是，C-42和C-43甲基连接到形式上衍生自相关扩链剂单元的羧基的位置。两种可能的生物合成模型可以假定占1的结构。整个糖苷配基骨架要么合成为一个连续系列的十三个丙二酰辅酶A和三个甲基丙二酰辅酶A延伸单元，这些单元在乙酰辅酶A起始单元上进行加工，要么糖苷配基骨架由三个单独的聚酮片段制成（C-13到C-34，C-41到Cl，和C-5到C-12）连接，使得中心片段（C-5到C-12）的有义性相对于其他片段是颠倒的。
Pulvomycin, 1, is a 22-membered macrocyclic polyketide natural product which can be isolated from the fermentative culture broth of Streptoverticillium netropis. The structure of pulvomycin was first reported in 1957.1 3A similar isolate, named labilomycin because of its instabil-ity, was isolated in 1963, 2 3 but was subsequently shown to be identical with pulvomycin. 4 The structure originally proposed for 1 was accepted for nearly 20 years before inconsistencies between the NMR spectra of 1 and its suggested structure were noted. 5 An accurate structure for 1 was determined by Smith and coworkers using a series of NMR and MS experiments. 5 The antibiotic has attracted interest because of its mode of action. Like most macrolides 1 inhibits prokaryotic protein synthesis. 1 is unusual, however, in that it acts by blocking the formation of a ternary complex between the prokaryotic elongation factor Tu, GTP, and the aminoacyPRNA. 6 On close inspection, the structure of 1 would appear to deviate from the classical polyketide biosynthetic model. 7***** Intriguingly, the C-42 and C-43 methyl groups are appended to positions formally derived from the carboxyl groups of the relevant extender units. Two possible biosynthetic models can be postulated to account for thestructure of 1. Either the entire aglycon backbone is synthesized as one contiguous series ofthirteen malonyl-CoA and three methylmalonyl-CoA extender units elaborated on an acetyl-CoA starter unit, or the aglycon backbone is made from three separate polyketide fragments (C-13 to C-34, C-41 to Cl, and C-5 to C-12) linked so that the sense of the central (C-5 to C-12) fragment was reversed with respect to the other frag-ments.