BIOSYNTHESIS OF THE LINCOMYCINS .1. STUDIES USING STABLE ISOTOPES ON THE BIOSYNTHESIS OF THE PROPYL-L-HYGRIC AND ETHYL-L-HYGRIC ACID MOIETIES OF LINCOMYCIN-A AND LINCOMYCIN-B
BIOSYNTHESIS OF THE LINCOMYCINS .1. STUDIES USING STABLE ISOTOPES ON THE BIOSYNTHESIS OF THE PROPYL-L-HYGRIC AND ETHYL-L-HYGRIC ACID MOIETIES OF LINCOMYCIN-A AND LINCOMYCIN-B
复制标题
DOI：
10.1021/ja00337a038
复制
发表时间：
1984-01-01
影响因子：
15
通讯作者：
HURLEY, LH
中科院分区：
文献类型：
--
作者：
BRAHME, NM;GONZALEZ, JE;HURLEY, LH
用氚和~(13)C标记的前体，结合~(13)C-核磁共振和质谱分析，研究了林可霉素A和B的丙基-L-水酸和L-乙基-水酸的生物合成。结果表明，酪氨酸可以通过多巴转化为芳环裂解的中间体，很可能是通过2，3-胞外的裂解反应。使用D-(13C6)葡萄糖结合分析林可霉素A和丙基-L-水酸的13C-13C自旋耦合模式的实验允许在林可霉素A的生物合成过程中保留在一起的碳原子的决定因素。葡萄糖通过糖酵解和己糖单磷酸分别转化为磷酸烯醇式丙酮酸和4-磷酸红烯醇酯，后者又通过莽草酸途径转化为酪氨酸，从而转化为多巴。在DOPA之后的后续反应与2，3-外标醇的裂解途径和蛋氨酸的C-1单元的加成一起产生丙基侧链的末端甲基。这些结果现在与从酪氨酸生物合成衍生的炭霉素、托迈霉素和西比洛霉素中发现的C2-和C3-脯氨酸部分的结果一致。
The biosynthesis of the propyl-L-hygric acid and ethyl-L-hygric acid moieties of lincomycins A and B were examined by using deuterated and 13C-labeled precursors in combination with 13C-NMR and mass spectral analysis. The results, using specifically deuterated tyrosine, DOPA and methionine, demonstrate that tyrosine is converted via DOPA to an intermediate that undergoes aromatic ring cleavage most probably via a 2,3-extradiol cleavage reaction. An experiment using D-(13C6)glucose in combination with analysis of the 13C-13C spin-coupling patterns in lincomycin A and propyl-L-hygric acid permits the determinant of those carbon atoms that remain together during the biosynthesis of lincomycin A. Glucose is converted via glycolysis and the hexose monophosphate shunt to phosphoenolpyruvate and erythrose 4-phosphate, respectively, which are in turn converted via the shikimic acid pathway to tyrosine and hence into DOPA. The subsequent reactions after DOPA are consisent with the 2,3-extradiol cleavage pathway and an addition of a C-1 unit from methionine to give rise to the terminal methyl group of the propyl side chain. These results are now consistent with those obtained for the C2- and C3-proline moieties found in anthramycin, tomaymycin and sibiromycin that also biosynthetically derived from tyrosine.