3-Hydroxy-3-methylglutaryl-coenzyme A (CoA) synthase is involved in biosynthesis of isovaleryl-CoA in the myxobacterium Myxococcus xanthus during fruiting body formation.
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.
Bode
Helge B
HB
Institut für Pharmazeutische Biotechnologie, Universität des Saarlandes, P.O. Box 151150, 66041 Saarbrücken, Germany. h.bode@mx.uni-saarland.de
Ring
Michael W
MW
Schwär
Gertrud
G
Kroppenstedt
Reiner M
RM
Kaiser
Dale
D
Müller
Rolf
R
D000214:Acyl Coenzyme A / Q000096:biosynthesis*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000032:analysis; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D045782:Hemiterpenes; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000235:genetics / Q000378:metabolism*; D016941:Myxococcus xanthus / Q000201:enzymology / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D010421:Pentanoic Acids; D012329:RNA, Bacterial / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D014158:Transcription, Genetic
D000214:Acyl Coenzyme A; D001426:Bacterial Proteins; D005227:Fatty Acids; D045782:Hemiterpenes; D010421:Pentanoic Acids; D012329:RNA, Bacterial; D012333:RNA, Messenger; C008216:isovaleric acid; C017447:isovaleryl-coenzyme A; D006904:Hydroxymethylglutaryl-CoA Synthase