Profiling a Taxol pathway 10beta-acetyltransferase: assessment of the specificity and the production of baccatin III by in vivo acetylation in E. coli

Chemistry & Biology
Catherine LoncaricKevin D Walker

Abstract

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.

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Citations

Nov 25, 2006·Applied Microbiology and Biotechnology·Dieter Frense
Aug 21, 2013·Journal of Industrial Microbiology & Biotechnology·Jian ZaiyouZhou Xiuren
Jun 10, 2014·Annual Review of Chemical and Biomolecular Engineering·Nidhi Tibrewal, Yi Tang
Jun 22, 2011·Chemical Society Reviews·Javier González-SabínFrancisca Rebolledo
May 26, 2018·Molecular Biotechnology·Shu-Ling LinPing-Lan Ouyang
May 26, 2018·Applied Biochemistry and Biotechnology·Lin-Feng YouJia-Jun Huang
Apr 23, 2009·Journal of the American Chemical Society·Danielle M NevarezKevin D Walker
Nov 15, 2008·Journal of the American Chemical Society·Mark E Ondari, Kevin D Walker

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