Fu H, McDaniel R, Hopwood D A, Khosla C
Department of Chemical Engineering, Stanford University, California 94305-5025.
Biochemistry. 1994 Aug 9;33(31):9321-6. doi: 10.1021/bi00197a036.
A genetically engineered strain expressing the essential components of the tetracenomycin polyketide synthase (tcm PKS) along with the actinorhodin ketoreductase (act KR) was found to produce two new (diastereomeric) aromatic polyketides, designated RM20b and RM20c, in addition to RM20, whose structure was reported earlier [McDaniel, R., Ebert-Khosla, S., Hopwood, D. A., & Khosla, C. (1993) Science 262, 1546-1550]. Spectroscopic and in vivo isotopic labeling analysis of RM20b and RM20c revealed that their polyketide backbones were identical to that of RM20 with respect to chain length, regiospecificity of ketoreduction, and regiospecificity of the first intramolecular aldol condensation. This is consistent with earlier predictions that the essential components of the PKS--a bifunctional ketosynthase/acyltransferase, a chain length determining factor, and an acyl carrier protein--are responsible for controlling each of these features of the polyketide backbone [McDaniel, R., Ebert-Khosla, S., Hopwood, D. A., & Khosla, C. (1993) Science 262, 1546-1550; McDaniel, R., Ebert-Khosla, S., Hopwood, D. A., & Khosla, C. (1993) J. Am. Chem. Soc. 115, 11671-11675; Fu, H., Ebert-Khosla, S., Hopwood, D. A., & Khosla, C. (1994) J. Am. Chem. Soc. 116, 4166-4170]. In addition, however, RM20b and RM20c possess two unusual features. In both molecules the hydroxyls on sp3 C-9 and C-7 of the first six-membered ring, which arise as a result of ketoreduction and aldol condensation, respectively, are intact, rather than being lost via dehydration. Furthermore, the relative yield of RM20b (in which these hydroxyls are syn) is 7-fold greater than that of RM20c (in which they are anti).(ABSTRACT TRUNCATED AT 250 WORDS)
一种基因工程菌株，其表达四环素聚酮合酶（tcm PKS）的必需组分以及放线紫红素酮还原酶（act KR），结果发现该菌株除了产生结构已于之前报道过的RM20 [麦克丹尼尔，R.，埃伯特 - 霍斯拉，S.，霍普伍德，D. A.，& 霍斯拉，C.（1993年）《科学》262卷，1546 - 1550页] 外，还产生了两种新的（非对映体）芳香族聚酮化合物，命名为RM20b和RM20c。对RM20b和RM20c的光谱分析及体内同位素标记分析表明，就链长、酮还原的区域特异性以及首次分子内羟醛缩合的区域特异性而言，它们的聚酮骨架与RM20的相同。这与之前的预测一致，即聚酮合酶的必需组分——一种双功能酮合成酶/酰基转移酶、一个链长决定因子和一个酰基载体蛋白——负责控制聚酮骨架的这些特征 [麦克丹尼尔，R.，埃伯特 - 霍斯拉，S.，霍普伍德，D. A.，& 霍斯拉，C.（1993年）《科学》262卷，1546 - 1550页；麦克丹尼尔，R.，埃伯特 - 霍斯拉，S.，霍普伍德，D. A.，& 霍斯拉，C.（1993年）《美国化学会志》115卷，11671 - 11675页；傅，H.，埃伯特 - 霍斯拉，S.，霍普伍德，D. A.，& 霍斯拉，C.（1994年）《美国化学会志》116卷，4166 - 4170页]。然而，此外，RM20b和RM20c具有两个不同寻常的特征。在这两种分子中，分别由酮还原和羟醛缩合产生的第一个六元环的sp3 C - 9和C - 7上的羟基是完整的，而不是通过脱水失去。此外，RM20b（其中这些羟基是顺式的）的相对产量比RM20c（其中它们是反式的）高7倍。（摘要截选至250词）
