An investigation of nitrile transforming enzymes in the chemo-enzymatic synthesis of the taxol sidechain

Wilding, Birgit, Veselá, Alicja, Perry, Justin, Black, Gary, Zhang, Meng, Martínková, Ludmila and Klempier, Norbert (2015) An investigation of nitrile transforming enzymes in the chemo-enzymatic synthesis of the taxol sidechain. Organic & Biomolecular Chemistry, 13 (28). pp. 7803-7812. ISSN 1477-0520

[img]
Preview
PDF
c5ob01191d.pdf - Published Version
Available under License Creative Commons Attribution.

Download (1MB) | Preview
Official URL: http://dx.doi.org/10.1039/C5OB01191D

Abstract

Paclitaxel (taxol) is an antimicrotubule agent widely used in the treatment of cancer. Taxol is prepared in a semisynthetic route by coupling the N-benzoyl-(2R,3S)-3-phenylisoserine sidechain to the baccatin III core structure. Precursors of the taxol sidechain have previously been prepared in chemoenzymatic approaches using acylases, lipases, and reductases, mostly featuring the enantioselective, enzymatic step early in the reaction pathway. Here, nitrile hydrolysing enzymes, namely nitrile hydratases and nitrilases, are investigated for the enzymatic hydrolysis of two different sidechain precursors. Both sidechain precursors, an openchain α-hydroxy-β-amino nitrile and a cyanodihydrooxazole, are suitable for coupling to baccatin III directly after the enzymatic step. An extensive set of nitrilases and nitrile hydratases was screened towards their activity and selectivity in the hydrolysis of two taxol sidechain precursors and their epimers. A number of nitrilases and nitrile hydratases converted both sidechain precursors and their epimers.

Item Type: Article
Subjects: F100 Chemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: Becky Skoyles
Date Deposited: 02 Jul 2015 15:01
Last Modified: 02 Nov 2017 11:49
URI: http://nrl.northumbria.ac.uk/id/eprint/23229

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics


Policies: NRL Policies | NRL University Deposit Policy | NRL Deposit Licence