ScbA from Streptomyces coelicolor A3(2) has homology to fatty acid synthases and is able to synthesize gamma-butyrolactones.
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.
Hsiao
Nai-Hua
NH
Mikrobiologie/Biotechnologie, Eberhard-Karls-Universität Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.
Söding
Johannes
J
Max-Planck-Institut für Entwicklungsbiologie, Spemannstr. 35, 72076 Tübingen, Germany.
Linke
Dirk
D
Max-Planck-Institut für Entwicklungsbiologie, Spemannstr. 35, 72076 Tübingen, Germany.
Lange
Corinna
C
Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745 Jena, Germany.
Hertweck
Christian
C
Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745 Jena, Germany.
Wohlleben
Wolfgang
W
Mikrobiologie/Biotechnologie, Eberhard-Karls-Universität Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.
Takano
Eriko
E
Mikrobiologie/Biotechnologie, Eberhard-Karls-Universität Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany.
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
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C446303:ScbA protein, Streptomyces; D064429:Fatty Acid Synthases; D015107:4-Butyrolactone