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Thiamin biosynthesis in prokaryotes
Authors:T P Begley  Diana M Downs  Steven E Ealick  Fred W McLafferty  Adolphus P G M Van Loon  Sean Taylor  Nino Campobasso  Hsiu-Ju Chiu  Cynthia Kinsland  Jason J Reddick  Jun Xi
Institution:(1) Department of Chemistry and Chemical Biology, 120 Baker Laboratory, Cornell University, Ithaca, NY 14853, USA e-mail: tpb2@cornell.edu Tel. +1-607-255-7133; Fax +1-607-255-4137, US;(2) Department of Bacteriology, University of Wisconsin-Madison, 1550 Linden Drive, Madison, WI 53706, USA, US;(3) Biotechnology Section, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, CH-4070 Basel, Switzerland, CH
Abstract:Twelve genes involved in thiamin biosynthesis in prokaryotes have been identified and overexpressed. Of these, six are required for the thiazole biosynthesis (thiFSGH, thiI, and dxs), one is involved in the pyrimidine biosynthesis (thiC), one is required for the linking of the thiazole and the pyrimidine (thiE), and four are kinase genes (thiD, thiM, thiL, and pdxK). The specific reactions catalyzed by ThiEF, Dxs, ThiDM, ThiL, and PdxK have been reconstituted in vitro and ThiS thiocarboxylate has been identified as the sulfur source. The X-ray structures of thiamin phosphate synthase and 5-hydroxyethyl-4-methylthiazole kinase have been completed. The genes coding for the thiamin transport system (thiBPQ) have also been identified. Remaining problems include the cloning and characterization of thiK (thiamin kinase) and the gene(s) involved in the regulation of thiamin biosynthesis. The specific reactions catalyzed by ThiC (pyrimidine formation), and ThiGH and ThiI (thiazole formation) have not yet been identified. Received: 23 August 1998 / Accepted: 16 January 1999
Keywords:Thiamin  Biosynthesis  Prokaryotes  Transport  Kinase  Mechanism  Structure
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