In vitro enzymatic synthesis of baccatin III with novel and cheap acetyl donors by the recombinant taxoid 10β-O-acetyl transferase

Abstract

Despite the importance of baccatin III as a precursor to paclitaxel, a widely used chemotherapeutic agent, efficient enzymatic synthesis methods are lacking. Therefore, in this study, the recombinant taxoid 10β-O-acetyl transferase was prepared to produce baccatin III in vitro. The recombinant enzyme could use vinyl acetate, butyl acetate, sec-butyl acetate, isobutyl acetate, amyl acetate, and isoamyl acetate as novel and cheap alternative acetyl group donors to replace the expensive acetyl CoA for the enzymatic synthesis of baccatin III. A molecular docking study further confirmed that these acetyl donors could reasonably bind to the enzyme molecule. Using the aqueous two-phase bio-catalytic reaction system, hexane and ethyl acetate could increase the yield of product baccatin III by 2.8% and 1.1% respectively. This approach using novel and cheap acetyl donors is promising for the enzymatic synthesis of baccatin III for the future industrial production of paclitaxel.

Keywords:

• Enzymatic synthesis
• taxoid 10β-O-acetyl transferase
• baccatin III
• acetyl group donors
• paclitaxel

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Science and Technology Program of Guangdong Province under Grant 2014B050505018, 2014B020205003; and the National Natural Science Foundation of China under Grant 31071837, 31372116, and 31572178.