title: ScbA from Streptomyces coelicolor A3(2) has homology to fatty acid synthases and is able to synthesize gamma-butyrolactones.
abstract: gamma-Butyrolactones play an important role in the regulation of antibiotic production and differentiation in Streptomyces. However the biosynthetic pathway for these small molecules has not yet been determined, and in vitro synthesis has not been reported. The function of the AfsA family of proteins, originally proposed to catalyse gamma-butyrolactone synthesis, has been in debate. To clarify the function of the AfsA family, and to understand the synthesis of the gamma-butyrolactones, we performed in silico analysis of this protein family. AfsA proteins consist of two divergent domains, each of which has similarity to the fatty acid synthesis enzymes FabA and FabZ. The two predicted active sites in ScbA, which is the AfsA orthologue found in Streptomyces coelicolor, were mutated, and gamma-butyrolactone biosynthesis was abolished in all four constructed mutants, strongly suggesting that ScbA has enzymic activity.
authors.affiliation: Mikrobiologie/Biotechnologie, Eberhard-Karls-Universität Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.
authors.forename: Nai-Hua
authors.initials: NH
authors.lastname: Hsiao
authors.affiliation: Max-Planck-Institut für Entwicklungsbiologie, Spemannstr. 35, 72076 Tübingen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Söding
authors.affiliation: Max-Planck-Institut für Entwicklungsbiologie, Spemannstr. 35, 72076 Tübingen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Linke
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745 Jena, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Lange
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745 Jena, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hertweck
authors.affiliation: Mikrobiologie/Biotechnologie, Eberhard-Karls-Universität Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wohlleben
authors.affiliation: Mikrobiologie/Biotechnologie, Eberhard-Karls-Universität Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.
authors.forename: Eriko
authors.initials: E
authors.lastname: Takano
mesh_terms: D015107:4-Butyrolactone / Q000096:biosynthesis*; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D064429:Fatty Acid Synthases / Q000235:genetics*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D048372:Streptomyces coelicolor / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C446303:ScbA protein, Streptomyces; D064429:Fatty Acid Synthases; D015107:4-Butyrolactone