O'Hagan D, Rogers S V, Duffin G R, Reynolds K A
Department of Chemistry, University of Durham, United Kingdom.
J Antibiot (Tokyo). 1995 Nov;48(11):1280-7. doi: 10.7164/antibiotics.48.1280.
Feeding experiments with isotopically labelled samples of [13C,2H3-methyl]-thymine, (R,S)-[I-13C]- and (R,S-[13C-methyl]-beta-aminoisobutyrates into monensin-A demonstrate that these metabolites can all contribute to the methylmalonyl-CoA pool in Streptomyces cinnamonensis, and implicate DNA catabolism as a contributory metabolic source of propionate carbon atoms for secondary metabolic biosynthesis. Further, these labelled compounds were unexpectedly incorporated into the butyrate unit of monensin-A, an observation which can be rationalised if beta-aminoisobutyrate is converted to methacrylyl-CoA and then reduced to isobutyryl-CoA prior to conversion to butyryl-Coa by the action of isobutyryl-CoA mutase. Feeding experiments with [I-13C]- and [13C-methyl]-methacrylates and [3-13C]-isobutyrate suggest that these metabolites partition similarly between the butyrate and propionate units of monensin-A consistent with the view that isobutyryl-CoA and methacrylyl-CoA have a close metabolic relationship.
用同位素标记的[13C,2H3 - 甲基] - 胸腺嘧啶、(R,S)-[I - 13C] - 和(R,S)-[13C - 甲基] - β - 氨基异丁酸酯对莫能菌素 - A进行饲喂实验表明，这些代谢物都可以对肉桂链霉菌中的甲基丙二酰辅酶A池有贡献，并表明DNA分解代谢是次级代谢生物合成中丙酸盐碳原子的一个代谢来源。此外，这些标记化合物意外地掺入到莫能菌素 - A的丁酸酯单元中，如果β - 氨基异丁酸酯在异丁酰辅酶A变位酶作用下转化为丁酰辅酶A之前先转化为甲基丙烯酰辅酶A然后还原为异丁酰辅酶A，那么这一观察结果就可以得到合理的解释。用[I - 13C] - 和[13C - 甲基] - 甲基丙烯酸酯以及[3 - 13C] - 异丁酸进行的饲喂实验表明，这些代谢物在莫能菌素 - A的丁酸酯和丙酸盐单元之间的分配类似，这与异丁酰辅酶A和甲基丙烯酰辅酶A具有密切代谢关系的观点一致。
