Nitric Oxide Synthases of Bacteria - and Other Unicellular Organisms

Abstract

The defining feature of a nitric oxide synthase (NOS) is a heme and pterin-binding oxygenase domain, and enzymes that possess this domain are found in animals and bacteria. While the roles of animal NOS in such processes as vasodilation, neurotransmission, and host defence are understandably important for multicellular life, they are meaningless in bacteria, which makes bacterial NOSs all the more interesting as objects of study. This review describes the structural similarities and differences between animal and bacterial NOS, and how such differences may influence the extent and duration of bacterial NO production, and, ultimately the roles of NO in microorganisms. Recent progress in defining the functions of bacterially-derived NO, notably in protection from various stresses and as a potential transcriptional regulator are described. Finally, an attempt is made to span the gap between animal and bacterial nitric oxide synthases by commenting on the search for examples of NOS in single-celled eukaryotes, where progress seems imminent. The story of nitric oxide synthase (NOS) is a wonderful example of how an enzyme's function can evolve over time, even as its structure and mechanism remain largely intact. Constitutive NOS isotypes of mammals are used for the transient production of nanomolar amounts of NO for neurotransmission and vasodilation, while at the higher concentrations produced by inducible NOS in macrophages over sustained periods, NO is cytotoxic and is used to kill pathogens. Yet the origin of NOS is ancient; since the turn of the century the number of bacteria known to carry a NOS gene has increased sharply, and the work of defining the roles of bacterial NOS is an active and exciting area of research. But the story of NOS is also the story of an enzyme that has been characterized mainly in these two distinct kingdoms, the metazoans (overwhelmingly of mammals) and the bacteria, with few studies from other branches of life. If the bacteria originated it and we still have it, why is it seemingly so rare elsewhere? If it can be found in other kingdoms, for example among the protists, what might its functions be? This brief review will begin with the features common to NOS and then, gradually, move towards their differences. This includes the biochemical targets of NO, the reaction catalyzed by NOS, common structural features and differences in the enzyme, and the different roles that these enzymes have, with the focus on bacterial NOSs. Having considered these aspects, the prospects of the presence of NOS in single-celled eukaryotes and their possible functions will be discussed, which, because of the paucity of