title: An investigation of nitrile transforming enzymes in the chemo-enzymatic synthesis of the taxol sidechain.
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.
authors.affiliation: acib GmbH (Austrian Centre of Industrial Biotechnology), c/o Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria. klempier@tugraz.at.
authors.forename: Birgit
authors.initials: B
authors.lastname: Wilding
authors.forename: Alicja B
authors.initials: AB
authors.lastname: Veselá
authors.forename: Justin J B
authors.initials: JJ
authors.lastname: Perry
authors.forename: Gary W
authors.initials: GW
authors.lastname: Black
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.forename: Ludmila
authors.initials: L
authors.lastname: Martínková
authors.forename: Norbert
authors.initials: N
authors.lastname: Klempier
mesh_terms: D000619:Aminohydrolases / Q000737:chemistry / Q000378:metabolism*; D006836:Hydro-Lyases / Q000737:chemistry / Q000378:metabolism*; D006868:Hydrolysis; D008968:Molecular Conformation; D009570:Nitriles / Q000737:chemistry / Q000378:metabolism*; D017239:Paclitaxel / Q000096:biosynthesis* / Q000737:chemistry
chemical_list: D009570:Nitriles; D000619:Aminohydrolases; C021867:nitrilase; D006836:Hydro-Lyases; C048831:nitrile hydratase; D017239:Paclitaxel