3 years ago

Improving 10-deacetylbaccatin III-10-β-O-acetyltransferase catalytic fitness for Taxol production

Improving 10-deacetylbaccatin III-10-β-O-acetyltransferase catalytic fitness for Taxol production
Hao Wang, Ting Gong, Jing-Jing Chen, Tian-Jiao Chen, Ping Zhu, Jin-Ling Yang, Bing-Juan Li
The natural concentration of the anticancer drug Taxol is about 0.02% in yew trees, whereas that of its analogue 7-β-xylosyl-10-deacetyltaxol is up to 0.5%. While this compound is not an intermediate in Taxol biosynthetic route, it can be converted into Taxol by de-glycosylation and acetylation. Here, we improve the catalytic efficiency of 10-deacetylbaccatin III-10-O-acetyltransferase (DBAT) of Taxus towards 10-deacetyltaxol, a de-glycosylated derivative of 7-β-xylosyl-10-deacetyltaxol to generate Taxol using mutagenesis. We generate a three-dimensional structure of DBAT and identify its active site using alanine scanning and design a double DBAT mutant (DBATG38R/F301V) with a catalytic efficiency approximately six times higher than that of the wild-type. We combine this mutant with a β-xylosidase to obtain an in vitro one-pot conversion of 7-β-xylosyl-10-deacetyltaxol to Taxol yielding 0.64 mg ml−1 Taxol in 50 ml at 15 h. This approach represents a promising environmentally friendly alternative for Taxol production from an abundant analogue.

Publisher URL: http://www.nature.com/articles/ncomms15544

DOI: 10.1038/ncomms15544

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