Abstract
Nikkomycins are peptidyl nucleoside antibiotics that act as therapeutic antifungal agents in humans and easily degraded insecticides in agriculture. The nikkomycin peptidyl moiety contains a pyridyl residue derived from L-lysine. The first step in peptidyl biosynthesis is an aminotransferase-catalyzed reaction that converts L-lysine to Delta(1)- or Delta(2)-piperideine-2-carboxylate (P2C). Spectral, chromatographic, and kinetic analyses show that the aerobic reaction of nikD with P2C results in the stoichiometric formation of picolinate, accompanied by the reduction of 2 mol of oxygen to hydrogen peroxide. A high resolution HPLC method, capable of separating picolinate, nicotinate and isonicotinate, was developed and used in product identification. NikD contains 1 mol of covalently bound FAD and exists as a monomer in solution. Reductive and oxidative titrations with dithionite and potassium ferricyanide, respectively, show that FAD is the only redox-active group in nikD. Anaerobic reaction of nikD with 1 mol of P2C results in immediate reduction of enzyme-bound FAD. Because nikD is an obligate 2-electron acceptor, it is proposed that the observed 4-electron oxidation of P2C to picolinate occurs via a mechanism involving two su...Continue Reading
References
Apr 1, 1979·Archives of Microbiology·G U Brillinger
May 1, 1991·Journal of Biochemistry·Y NishinaK Shiga
Jun 1, 1989·The Journal of Antibiotics·C BormannH Zähner
May 15, 1985·Archives of Biochemistry and Biophysics·C Gomez-Moreno, D E Edmondson
Jan 1, 1993·Clinical Microbiology Reviews·R F Hector
Aug 29, 1997·The Journal of Biological Chemistry·A A Raibekas, V Massey
Jul 11, 1998·European Journal of Biochemistry·C Bruntner, C Bormann
Mar 10, 2001·Journal of Chromatography. B, Biomedical Sciences and Applications·C DazziL Varesio
Aug 10, 2002·Journal of Bacteriology·Wises NamwatTakuya Nihira
Citations
Apr 27, 2005·Biochemistry·Alshaimaa Hassan-AbdallahMarilyn Schuman Jorns
Jan 17, 2007·Biochemistry·Robert C BrucknerMarilyn Schuman Jorns
Apr 10, 2009·Biochemistry·Robert C Bruckner, Marilyn Schuman Jorns
Jun 18, 2009·Biochemistry·Phaneeswara-Rao KommojuMarilyn Schuman Jorns
Aug 26, 2009·Biochemistry·Phaneeswara-Rao KommojuMarilyn Schuman Jorns
May 19, 2012·Journal of the American Chemical Society·Xudong QuWen Liu
Apr 23, 2014·Microbial Cell Factories·Chi FengHuarong Tan
Apr 28, 2005·Molecular Microbiology·Neil R WilliamsonGeorge P C Salmond
Sep 3, 2011·The FEBS Journal·Alexandra BinterPeter Macheroux
Aug 29, 2006·Journal of Molecular Biology·Robert M G HynsonMarilyn Schuman Jorns
Feb 9, 2006·Metabolic Engineering·Guoqing NiuHuarong Tan
Jun 1, 2005·Protein Expression and Purification·Alshaimaa Hassan-AbdallahMarilyn Schuman Jorns
Aug 19, 2007·Structure·Christopher J CarrellF Scott Mathews
Jan 30, 2010·Natural Product Reports·Michael WinnTimothy D H Bugg
May 18, 2012·Organic Letters·Yiguang ZhuChangsheng Zhang
Oct 27, 2015·Chemistry & Biology·Meinan LvYi Yu
Oct 6, 2005·Chembiochem : a European Journal of Chemical Biology·Cristian GinjPeter Macheroux
Aug 9, 2017·Science China. Life Sciences·Guoqing NiuHuarong Tan
Dec 20, 2018·Organic & Biomolecular Chemistry·Xuan YunYi Yu
Jan 7, 2021·Natural Product Reports·M McErleanS G Van Lanen
Apr 5, 2021·Archives of Biochemistry and Biophysics·Majd LahhamSilvia Wallner