MACROLIDE BIOSYNTHESIS .7. INCORPORATION OF POLYKETIDE CHAIN ELONGATION INTERMEDIATES INTO METHYMYCIN
MACROLIDE BIOSYNTHESIS .7. INCORPORATION OF POLYKETIDE CHAIN ELONGATION INTERMEDIATES INTO METHYMYCIN
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DOI：
10.1021/ja00055a023
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发表时间：
1993-01-27
影响因子：
15
通讯作者：
OTT, WR
中科院分区：
文献类型：
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作者：
CANE, DE;LAMBALOT, RH;OTT, WR
将[1-C-13]丙酸盐施用到委内瑞拉链霉菌 SC 2366 培养物中会产生甲霉素 (1)，通过 C-13 NMR 分析表明甲霉素在预测位点 C-1、C-3、C-5、C-9 和 C-11 处被标记。类似地，掺入[1,2-C-13(2)]乙酸酯得到在C-7和C-8处标记的甲霉素。一系列推测的聚酮化合物链延长中间体也被成功掺入。因此，补加 (2S,3R)-[2,3-C-13(2)]-2-甲基-3-羟基戊酰基 N-乙酰半胱胺 (NAC) 硫酯 7a 得到了如预期在 C-10 和 C-11 处标记的甲霉素 (1) 和新甲霉素 (2)。在补充实验中，将(2S,3R)-[3-H-2,3-C-13]-2-甲基-3-羟基戊酰基NAC硫酯7b掺入1和2中，而没有损失氘。最后，掺入(4R,5R)-[2,3-C-13(2)]-4-甲基-5-羟基-2-庚烯酰基NAC硫酯10a得到在C-8和C-9处标记的1和2。这些结果支持聚酮化合物链组装的过程模型，其中在每个缩合步骤之后调整官能度和氧化水平。
Administration of [1-C-13] propionate to cultures of Streptomyces venezuelae SC 2366 gave methymycin (1), which was shown by C-13 NMR analysis to be labeled at the predicted sites, C-1, C-3, C-5, C-9, and C-11. Similarly, incorporation of [1,2-C-13(2)]acetate gave methymycin labeled at C-7 and C-8. A series of presumptive intermediates of polyketide chain elongation was also successfully incorporated. Thus, feeding of (2S,3R)-[2,3-C-13(2)]-2-methyl-3-hydroxypentanoyl N-acetylcysteamine (NAC) thioester 7a gave both methymycin (1) and neomethymycin (2) labeled as expected at C-10 and C-11. In a complementary experiment, (2S,3R)-[3-H-2,3-C-13]-2-methyl-3-hydroxypentanoyl NAC thioester 7b was incorporated into 1 and 2 without loss of deuterium. Finally, incorporation of (4R,5R)-[2,3-C-13(2)]-4-methyl-5-hydroxy-2-heptenoyl NAC thioester 10a gave 1 and 2 labeled at C-8 and C-9. These results support a processive model of polyketide chain assembly in which the functionality and oxidation level are adjusted subsequent to each condensation step.