Zumft WG
The biological role of nitric oxide in bacteria
Arch Microbiol 160:253-264 (1993)

Introduction
Bacterial N oxide metabolism is related to cellular bioenergetics and processes of nitrogen assimilation. The interest in nitric oxide (NO) centers around the dissimilatory transformation of nitrate, better known as the denitrification process. Denitrification [described as phenomenon more than 100 years ago (Gayon and Dupetit 1886)], is a distinctive mode of respiration that satisfies the bioenergetic needs of a great variety of bacteria by transforming oxyanions of nitrogen to N2, mainly under conditions of reduced oxygen tension or strict anaerobiosis. The reaction reverses nitrogen fixation in the biogeochemical N cycle sustained by prokaryotes. Denitrification is controlled by the metalloenzymes nitrate reductase, nitrite reductase, nitric oxide reductase, and nitrous oxide (N2O) reductase and involves the corresponding enzyme substrates. The same magnitude of nitrogen fixed yearly by biological and abiological processes [combined estimates vary between 254 to 406 million tons N (Jenkinson 1990)] has to be returned to Nby denitrification to close the N cycle. However, because of the large anthropogenic contribution, fixation and denitrification are not balanced anymore as evident from the steady increase of nitrate in the environment. A second concern focussing around NO and the conditions of its microbial formation, is the nitrosation of secondary amines in the etiology of certain types of cancer. Since the discovery of NO in 1987 as a vasodilatory messenger (Ignarro et al. 1987; Palmer et al. 1987), the biomedical community is astounded by the diverse roles of NO in cellular communication including the central and peripheral nervous system, and in host defense mechanisms of eukaryotes (for reviews see Marletta et al. 1990; Moncada 1992; Nathan 1992; Traylor and Sharma 1992; Edelman and Gaily 1992). Yet NO is not an obscure chemical and certainly no newcomer to the life sciences, as often stated in hyperbole. Early in evolution NO took its role as a central player in bacterial bioenergetics and in the global N cycle vital to all organisms. The chemistry of NO in biological systems and that of the nitroxyl anion (NO-) and nitrosonium cation (NO+) has been reviewed briefly (Stamler et al. 1992c; see also comment by Bonner and Hughes 1993). Another remarkable finding is the formation of N2O from nitrite, sometimes accompanied by NO production, by the fungus imperfectus Fusarium oxysporum and telemorphic and anamorphic relatives (Shoun et al. 1992). These fungi synthesize a special cytochrome P-450 induced only in the presence of nitrite (Shoun and Tanimoto 1991), which has been shown to have NO reductase activity (Nakahara et al. 1993). The existence of such a hemoprotein is of interest in the context that the cytokine (interferon-g and lipopolysaccharide)-inducible form of NO synthase from macrophages is a cytochrome P-450 (White and Marletta 1992); also hepatic cytochrome P-450 monooxygenases are able to convert the NG-hydroxy-activated form of L-arginine to NO (Boucher et al. 1992). In another fungus, the slime mold Dictyostelium discoideum, NO alters the cellular aggregation behavior via ADP-ribosylation of a cytoplasmic 41-kDa protein (Tao et al. 1992). Principles of bacterial NO metabolism were spelled out nearly 40 years ago. NO was found as a product of denitrification from a clay loam microcosm with 15N nitrate as tracer (Wijler and Delwiche 1954). The study of nitrite utilization with Thiobacillus denitrificans established that NO was consumed and produced by a defined axenic culture (Baalsrud and Baalsrud 1954). NO was given status of an intermediate in bacterial denitrification, first as the result of studies with intact cells (Iwasaki et al. 1956; Matsubara and Mori 1968) and later from recognition that cell-free extracts of "Pseudomonas denitrificans" reduce exogenous NO (Miyata et al. 1969). Around that time Pseudomonas stutzeri ZoBell (formerly P. perfectomarina) was introduced to denitrification research and a pathway identical to that of Mori and coworkers was formulated (Payne et al. 1971):

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