A biosynthetic pathway to isovaleryl-CoA in myxobacteria: the involvement of the mevalonate pathway.
A biosynthetic shunt pathway branching from the mevalonate pathway and providing starter units for branched-chain fatty acid and secondary metabolite biosynthesis has been identified in strains of the myxobacterium Stigmatella aurantiaca. This pathway is upregulated when the branched-chain alpha-keto acid dehydrogenase gene (bkd) is inactivated, thus impairing the normal branched-chain amino acid degradation process. We previously proposed that, in this pathway, isovaleryl-CoA is derived from 3,3-dimethylacrylyl-CoA (DMA-CoA). Here we show that DMA-CoA is an isomerization product of 3-methylbut-3-enoyl-CoA (3MB-CoA). This compound is directly derived from 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) by a decarboxylation/ dehydration reaction resembling the conversion of mevalonate 5-diphosphate to isopentenyl diphosphate. Incubation of cell-free extracts of a bkd mutant with HMG-CoA gave product(s) with the molecular mass of 3MB-CoA or DMA-CoA. The shunt pathway most likely also operates reversibly and provides an alternative source for the monomers of isoprenoid biosynthesis in myxobacteria that utilize L-leucine as precursor.
Mahmud
Taifo
T
College of Pharmacy, Oregon State University, Corvallis, OR 97331-3507, USA. taifo.mahmud@orgenstate.edu
Wenzel
Silke C
SC
Wan
Eva
E
Wen
Kwun Wah
KW
Bode
Helge B
HB
Gaitatzis
Nikolaos
N
Müller
Rolf
R
D000214:Acyl Coenzyme A / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D005977:Glutarates / Q000737:chemistry / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008689:Methacrylates; D008798:Mevalonic Acid / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D009231:Myxococcales / Q000737:chemistry / Q000378:metabolism*; D011804:Quinolines / Q000737:chemistry / Q000378:metabolism; D020606:Stigmatella aurantiaca / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013844:Thiazoles / Q000737:chemistry / Q000378:metabolism
D000214:Acyl Coenzyme A; D005977:Glutarates; D008689:Methacrylates; D011804:Quinolines; D013844:Thiazoles; C052094:aurachin A; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; C022034:3-methylglutaconic acid; C017447:isovaleryl-coenzyme A; C030517:myxothiazol; D007930:Leucine; D008798:Mevalonic Acid