title: Bacterial nitric-oxide synthases operate without a dedicated redox partner.
abstract: Bacterial nitric-oxide (NO) synthases (bNOSs) are smaller than their mammalian counterparts. They lack an essential reductase domain that supplies electrons during NO biosynthesis. This and other structural peculiarities have raised doubts about whether bNOSs were capable of producing NO in vivo. Here we demonstrate that bNOS enzymes from Bacillus subtilis and Bacillus anthracis do indeed produce NO in living cells and accomplish this task by hijacking available cellular redox partners that are not normally committed to NO production. These "promiscuous" bacterial reductases also support NO synthesis by the oxygenase domain of mammalian NOS expressed in Escherichia coli. Our results suggest that bNOS is an early precursor of eukaryotic NOS and that it acquired its dedicated reductase domain later in evolution. This work also suggests that alternatively spliced forms of mammalian NOSs lacking their reductase domains could still be functional in vivo. On a practical side, bNOS-containing probiotic bacteria offer a unique advantage over conventional chemical NO donors in generating continuous, readily controllable physiological levels of NO, suggesting a possibility of utilizing such live NO donors for research and clinical needs.
authors.affiliation: Department of Biochemistry, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Ivan
authors.initials: I
authors.lastname: Gusarov
authors.forename: Marina
authors.initials: M
authors.lastname: Starodubtseva
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Lindsey
authors.initials: L
authors.lastname: McQuade
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lippard
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Stuehr
authors.forename: Evgeny
authors.initials: E
authors.lastname: Nudler
mesh_terms: D000818:Animals; D001412:Bacillus subtilis / Q000201:enzymology* / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D010105:Oxygenases / Q000235:genetics / Q000378:metabolism; D010802:Phylogeny; D013379:Substrate Specificity
chemical_list: D009569:Nitric Oxide; D010105:Oxygenases; D019001:Nitric Oxide Synthase