BIOSYNTHESIS OF NCS CHROM-A, THE CHROMOPHORE OF THE ANTITUMOR ANTIBIOTIC NEOCARZINOSTATIN
BIOSYNTHESIS OF NCS CHROM-A, THE CHROMOPHORE OF THE ANTITUMOR ANTIBIOTIC NEOCARZINOSTATIN
复制标题
DOI：
10.1021/ja00191a028
复制
发表时间：
1989-04-26
影响因子：
15
通讯作者：
GOLDBERG, IH
中科院分区：
文献类型：
--
作者：
HENSENS, OD;GINER, JL;GOLDBERG, IH
采用单、双13C标记的乙酸前体和放射性标记的[甲基3h]蛋氨酸、[14C]碳酸氢钠和[14C]乙酸钠，通过卡兹酸链霉菌（ATCC #15944 F-42）进行了新卡兹酸抑素发色群A （NCS Chrom A）的生物合成研究。结果表明，聚焦胺的n -甲基和环烷酸部分的o -甲基是通过s -腺苷甲硫氨酸和碳酸盐中的环碳酸羰基碳得到的蛋氨酸。乙酸掺入结果表明，C12环烷酸环是由一个己基酸衍生而来。另一方面，令人感兴趣的C14环碳酸酯/双环[7.3.0]十二烯二炔环体系似乎是由至少8个头尾耦合的乙酸单元衍生而来的，这是根据聚乙炔的油酸-crepenynate生物合成途径进行讨论的。埃斯佩霉素/卡利奇霉素类抗肿瘤抗生素中相关的C15烯二炔环骨架可能类似地衍生。这些结合实验为NCS Chrom A史无前例的结构提供了独立的支持。
Biosynthetic studies on neocarzinostatin chromophore A (NCS Chrom A) were carried out on the basis of the incorporation of singly and doubly 13C labeled acetate precursors as well as radiolabeled [methyl-3H]methionine, [14C]sodium bicarbonate, and [14C]sodium acetate by cultures of Streptomyces carzinostaticus (ATCC #15944 F-42). The results suggest that the N-methyl of the fucosamine and the O-methyl of the naphthoic acid moieties are derived from methionine via S-adenosylmethionine and the cyclic carbonate carbonyl carbon from carbonate. The acetate incorporation results show that the C12 naphthoic acid ring is derived from a hexaketide. The intriguing C14 cyclic carbonate/bicyclo[7.3.0]dodecadienediyne ring system, on the other hand, appears to be derived from a minimum of eight head to tail coupled acetate units which is discussed in terms of the oleate-crepenynate biosynthetic pathway for polyacetylenes. The related C15 enediyne ring skeleton in the esperamicin/calicheamicin class of antitumor antibiotics may be similarly derived. These incorporation experiments provide independent support for the unprecedented structure of NCS Chrom A.