Regio‐ and stereoselective hydroxylation of taxoids by filamentous fungi

Abstract

Paclitaxel (Taxol), is one of the most promising chemotherapeutic agents developed for cancer treatment in past two decades. Microorganisms such as filamentous fungi are known to perform regio- and stereoselective hydroxylation of taxoids. Herein, we describe highly regio- and stereoselective hydroxylation at the 1beta and 9alpha positions of the taxane skeleton. Such hydroxylation reactions proceed readily for the taxadienes as substrates rather than taxoids having an oxetane ring. The presence of different oxygen substituents on the taxane nucleus, such as 5-acetoxy, has a significant effect on the selectivity and yield of the hydroxylation catalyzed by the microbial oxidases.

Conversion of 7‐deoxy‐10‐deacetylbaccatin‐III into 6‐α‐hydroxy‐7‐deoxy‐10‐deacetylbaccatin‐III byNocardioides luteus

“…Hydroxylation of taxadienes by filamentous fungi at the 6‐position and other positions has been reported by Hu and co‐workers [36–42]; however, fungal hydroxylation of taxanes having an oxetane ring was not reported. Hydroxylation of paclitaxel by a Streptomyces sp.…”

Determination of steroid hydroxylation specificity of an industrial strain Aspergillus ochraceus TCCC41060 by cytochrome P450 gene CYP68J5

“…Microbial transformations have proven to be an efficient alternative to chemical methods in the regio-and stereoselective functionalizations of steroid drugs (Borges et al 2009;Donova and Egorova 2012). But often low specificity and productivity associated with biotransformation severely limit their industrial applications because of low yields and expensive downstream purification (Collins et al 2001;Hu et al 2002). As a result, engineering highly efficient industrial strains are often required to implement a more economical production process.…”