Mikami Y, Takahashi K, Yazawa K, Arai T, Namikoshi M, Iwasaki S, Okuda S
J Biol Chem. 1985 Jan 10;260(1):344-8.
The biosynthesis of saframycin A, a heterocyclic quinone antitumor antibiotic isolated from Streptomyces lavendulae 314, was studied by feeding experiments with 14C and 13C precursors. Highly increased production of saframycin A and prolongation of the maximum production period of saframycin A were attained by constant pH control of the culture and by addition of chloramphenicol to the culture. The biosynthetic origin of the quinone skeleton common to the saframycin group was confirmed to be two tyrosine molecules which condense to generate the basic ring system of saframycin A. Feeding experiments with [1-13C]tyrosine showed specific labeling of C-11 and C-21 carbons of saframycin A, and the enrichment of the carbons was 40-fold over natural abundance. Two O- and two C-methyl and one N-methyl carbons arose directly from methionine, and alanine and glycine were the precursors for the pyruvoyl amide side chain of saframycin A.
从淡紫色链霉菌314中分离得到的杂环醌类抗肿瘤抗生素沙弗霉素A的生物合成，通过用14C和13C前体进行饲喂实验进行了研究。通过对培养物进行恒定pH控制以及向培养物中添加氯霉素，实现了沙弗霉素A产量的大幅提高和沙弗霉素A最大生产期的延长。已证实沙弗霉素类共有的醌骨架的生物合成起源是两个酪氨酸分子，它们缩合生成沙弗霉素A的基本环系。用[1-13C]酪氨酸进行的饲喂实验表明，沙弗霉素A的C-11和C-21碳有特异性标记，且这些碳的丰度比自然丰度高40倍。两个氧甲基、两个碳甲基和一个氮甲基碳直接来自甲硫氨酸，丙氨酸和甘氨酸是沙弗霉素A的丙酮酰酰胺侧链的前体。
