title: Biosynthesis of quinoxaline antibiotics: purification and characterization of the quinoxaline-2-carboxylic acid activating enzyme from Streptomyces triostinicus.
abstract: A quinoxaline-2-carboxylic acid activating enzyme was purified to homogeneity from triostin-producing Streptomyces triostinicus. It could also be purified from quinomycin-producing Streptomyces echinatus. Triostins and quinomycins are peptide lactones that contain quinoxaline-2-carboxylic acid as chromophoric moiety. The enzyme catalyzes the ATP-pyrophosphate exchange reaction dependent on quinoxaline-2-carboxylic acid and the formation of the corresponding adenylate. Besides quinoxaline-2-carboxylic acid, the enzyme also catalyzes the formation of adenylates from quinoline-2-carboxylic acid and thieno[3,2-b]pyridine-5-carboxylic acid. No adenylates were seen from quinoline-3-carboxylic acid, quinoline-4-carboxylic acid, pyridine-2-carboxylic acid, and 2-pyrazinecarboxylic acid. Previous work [Gauvreau, D., & Waring, M. J. (1984) Can. J. Microbiol. 30, 439-450] revealed that quinoline-2-carboxylic acid and thieno[3,2-b]pyridine-5-carboxylic acid became efficiently incorporated into the corresponding quinoxaline antibiotic analogues in vivo. Together with the data described here, this suggests that the enzyme is part of the quinoxaline antibiotics synthesizing enzyme system. The enzyme displays a native molecular weight of 42,000, whereas in its denatured form it is a polypeptide of Mr 52,000-53,000. It resembles in its behavior actinomycin synthetase I, the chromophore activating enzyme involved in actinomycin biosynthesis [Keller, U., Kleinkauf, H., & Zocher, R. (1984) Biochemistry 23, 1479-1484].
authors.affiliation: Institut für Biochemie und Molekulare Biologie, Technische Universität Berlin, Federal Republic of Germany.
authors.forename: K
authors.initials: K
authors.lastname: Glund
authors.forename: W
authors.initials: W
authors.lastname: Schlumbohm
authors.forename: M
authors.initials: M
authors.lastname: Bapat
authors.forename: U
authors.initials: U
authors.lastname: Keller
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000096:biosynthesis*; D002250:Carbon Radioisotopes; D002850:Chromatography, Gel; D002852:Chromatography, Ion Exchange; D004591:Electrophoresis, Polyacrylamide Gel; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D008970:Molecular Weight; D010453:Peptide Synthases / Q000302:isolation & purification / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D011810:Quinoxalines / Q000378:metabolism*; D013302:Streptomyces / Q000201:enzymology* / Q000254:growth & development; D013379:Substrate Specificity
chemical_list: D000900:Anti-Bacterial Agents; D002250:Carbon Radioisotopes; D010761:Phosphorus Radioisotopes; D011810:Quinoxalines; D000255:Adenosine Triphosphate; D008715:Methionine; D010453:Peptide Synthases; C064585:quinoxaline-2-carboxylic acid activating enzyme