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Microbiology 153 (2007), 1394-1404; DOI  10.1099/mic.0.2006/004432-0
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Microbiology 153 (2007), 1394-1404; DOI  10.1099/mic.0.2006/004432-0
© 2007 Society for General Microbiology

ScbA from Streptomyces coelicolor A3(2) has homology to fatty acid synthases and is able to synthesize {gamma}-butyrolactones

Nai-Hua Hsiao1,{dagger}, Johannes Söding2, Dirk Linke2, Corinna Lange3, Christian Hertweck3, Wolfgang Wohlleben1 and Eriko Takano1,{dagger}

1 Mikrobiologie/Biotechnologie, Eberhard-Karls-Universität Tübingen, Auf der Morgenstelle 28, 72076 Tübingen, Germany
2 Max-Planck-Institut für Entwicklungsbiologie, Spemannstr. 35, 72076 Tübingen, Germany
3 Leibniz Institute for Natural Product Research and Infection Biology, HKI, Beutenbergstr. 11a, 07745 Jena, Germany

Correspondence
Eriko Takano
e.takano{at}rug.nl

{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.


Abbreviations: SCB, Streptomyces coelicolor butyrolactones; VB, virginiae butanolide

Full details of the construction of ScbA mutants and further MS data are available as supplementary data with the online version of this paper.

{dagger}Present address: Department of Microbial Physiology, GBB, University of Groningen, Kerklaan 30, 9751NN, Haren, The Netherlands.







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