Loncaric Catherine, Merriweather Erin, Walker Kevin D
Department of Chemistry, Michigan State University, East Lansing, Michigan 48824, USA.
Chem Biol. 2006 Mar;13(3):309-17. doi: 10.1016/j.chembiol.2006.01.006.
The 10beta-acetyltransferase on the biosynthetic pathway of the antineoplastic drug Taxol catalyzes the regiospecific transfer of the acetyl group of acetyl-coenzyme A (CoA) to 10-deacetylbaccatin III. We demonstrate that in addition to acetyl group transfer, the overexpressed enzyme also catalyzes the exchange of propionyl and n-butyryl from the corresponding CoA thioester to the hydroxyl group at C10 of the cosubstrate. Also, in vivo studies revealed that E. coli, producing endogenous acetyl-CoA and overexpressing the recombinant acetyltransferase, can convert exogenously supplied 10-deacetylbaccatin III to baccatin III. Potentially, this heterologous in vivo production method in bacteria could be optimized to couple various unnatural acyl-CoA analogs to myriad amino and/or hydroxyl acceptors by acyltransferase catalysis; conceivably, this process could facilitate the preparation of second-generation Taxols.
抗肿瘤药物紫杉醇生物合成途径中的10β-乙酰转移酶催化乙酰辅酶A（CoA）的乙酰基区域特异性转移至10-去乙酰巴卡亭III。我们证明，除了乙酰基转移外，过表达的该酶还催化丙酰基和正丁酰基从相应的CoA硫酯交换至共底物C10位的羟基上。此外，体内研究表明，产生内源性乙酰CoA并过表达重组乙酰转移酶的大肠杆菌能够将外源供应的10-去乙酰巴卡亭III转化为巴卡亭III。潜在地，这种细菌中的异源体内生产方法可以进行优化，通过酰基转移酶催化将各种非天然酰基-CoA类似物与多种氨基和/或羟基受体偶联；可以想象，这个过程可能有助于第二代紫杉醇的制备。
