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Journal of Bacteriology, September 2006, p. 6524-6528, Vol. 188, No. 18
0021-9193/06/$08.00+0     doi:10.1128/JB.00825-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

3-Hydroxy-3-Methylglutaryl-Coenzyme A (CoA) Synthase Is Involved in Biosynthesis of Isovaleryl-CoA in the Myxobacterium Myxococcus xanthus during Fruiting Body Formation

Helge B. Bode,1* Michael W. Ring,1 Gertrud Schwär,1 Reiner M. Kroppenstedt,2 Dale Kaiser,3 and Rolf Müller1*

Institut für Pharmazeutische Biotechnologie, Universität des Saarlandes, 66041 Saarbrücken, Germany,1 Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ), 38124 Braunschweig, Germany,2 Departments of Biochemistry and Developmental Biology, Stanford University, Stanford, California 943053

Received 9 June 2006/ Accepted 7 July 2006

Isovaleryl-coenzyme A (IV-CoA) is the starting unit for some secondary metabolites and iso-odd fatty acids in several bacteria. According to textbook biochemistry, IV-CoA is derived from leucine degradation, but recently an alternative pathway that branches from the well-known mevalonate-dependent isoprenoid biosynthesis has been described for myxobacteria. A double mutant was constructed in Myxococcus xanthus by deletion of genes involved in leucine degradation and disruption of mvaS encoding the 3-hydroxy-3-methylglutaryl-coenzyme A synthase. A dramatic decrease of IV-CoA-derived iso-odd fatty acids was observed for the mutant, confirming mvaS to be involved in the alternative pathway. Additional quantitative real-time reverse transcription-PCR experiments indicated that mvaS is transcriptionally regulated by isovalerate. Furthermore, feeding studies employing an intermediate specific for the alternative pathway revealed that this pathway is induced during fruiting body formation, which presumably increases the amount of IV-CoA available when leucine is limited.


* Corresponding author. Mailing address: Institut für Pharmazeutische Biotechnologie, Universität des Saarlandes, P.O. Box 151150, 66041 Saarbrücken, Germany. Phone for Helge B. Bode: 49 681 302 5494. Fax: 49 681 302 5473. E-mail: h.bode{at}mx.uni-saarland.de. Phone for Rolf Müller: 49 681 302 5474. Fax: 49 681 302 5473. E-mail: rom{at}mx.uni-saarland.de.


Journal of Bacteriology, September 2006, p. 6524-6528, Vol. 188, No. 18
0021-9193/06/$08.00+0     doi:10.1128/JB.00825-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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