Differentiating the biosynthesis of pseudomonic acids A and B

Differentiating the biosynthesis of pseudomonic acids A and B
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DOI:
10.7164/antibiotics.54.166
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发表时间:
2001-02-01
影响因子:
3.3
通讯作者:
Teo, VK
Teo, VK
中科院分区:
医学4区
文献类型:
--
作者:
Mantle, PG;De Langen, M;Teo, VK

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假单胞菌酸A(1)是由荧光假单胞菌产生的主要商业假单胞菌酸抗生素。在特定的摇瓶条件下,1的初始发酵积累之后是8-羟基衍生物假单胞菌酸B的优先积累(2)。在发酵的早期、中期和后期,用[1-C-14]乙酸盐或L-[甲基-C-14]蛋氨酸脉冲进行生物合成探测,得到1和2中放射性的相对模式,这与2由1氧化产生或1由2还原形成的假设不一致。由于[甲基-C-14]甲硫氨酸仅标记假单胞菌酸盐分子的I:he 12-碳部分(被认为是早期生物合成部分)中的碳,因此放射性标记实验的证据表明,该生物合成中间体的优先早期氧化导致途径转向蓄积2而不是1。
Pseudomonic acid A (1) has been the dominant commercial pseudomonate antibiotic produced by Pseudomonas fluorescens. In specific shaken flask conditions initial fermentation accumulation of 1 is followed by preferential accumulation of the 8-hydroxy derivative, pseudomonic acid B (2). Biosynthetic probing with a pulse of [1-C-14] acetate or L-[methyl-C-14] methionine at early, mid and late stages of the fermentation gave relative patterns of radioactivity in 1 and 2 that are inconsistent with an assumption that 2 arises by oxidation of 1, or that 1 is formed by reduction of 2. Since [methyl-C-14] methionine only labels carbons in I:he 12-carbon part of the pseudomonate molecule that is thought to be an early biosynthetic moiety, the evidence from radiolabelling experiments implies that preferential early oxidation of this biosynthetic intermediate causes the pathway diversion to accumulate 2 instead of 1.