Nikkomycin biosynthesis: formation of a 4-electron oxidation product during turnover of NikD with its physiological substrate

Biochemistry
Robert C BrucknerM S Jorns

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

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Citations

Apr 23, 2014·Microbial Cell Factories·Chi FengHuarong Tan
Aug 29, 2006·Journal of Molecular Biology·Robert M G HynsonMarilyn Schuman Jorns
Jun 1, 2005·Protein Expression and Purification·Alshaimaa Hassan-AbdallahMarilyn Schuman Jorns
May 18, 2012·Organic Letters·Yiguang ZhuChangsheng Zhang
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
Apr 5, 2021·Archives of Biochemistry and Biophysics·Majd LahhamSilvia Wallner

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