Precursor supply for polyketide biosynthesis: the role of crotonyl-CoA reductase.
Crotonyl-CoA reductase (CCR), which catalyzes the reduction of crotonyl-CoA to butyryl-CoA, is common to most streptomycetes and appears to be inducible by either lysine or its catabolites in Streptomyces cinnamonensis grown in chemically defined medium. A major role of CCR in providing butyryl-CoA from acetate for monensin A biosynthesis has been demonstrated by the observation of a change in the monensin A/monensin B ratio in the parent C730.1 strain (50/50) and a ccr (encoding CCR) disruptant (12:88) of S. cinnamonensis in a complex medium. Both strains produce significantly higher monensin A/monensin B ratios in a chemically defined medium containing valine as a major carbon source than in either complex medium or chemically defined medium containing alternate amino acids. This observation demonstrates that under certain growth conditions valine catabolism may have a more significant role than CCR in providing butyryl-CoA. Such a process most likely involves an isomerization of the valine catabolite isobutyryl-CoA, catalyzed by the coenzyme B(12)-dependent isobutyryl-CoA mutase. Monensin labeling experiments using dual (13)C-labeled acetate in the ccr-disrupted S. cinnamonensis indicate the presence of an additional coenzyme B(12)-dependent mutase linking branched and straight-chain C(4) compounds by a new pathway.
Liu
H
H
Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, Virginia 23219, USA.
Reynolds
K A
KA
D019342:Acetic Acid / Q000378:metabolism; D000214:Acyl Coenzyme A / Q000378:metabolism / Q000502:physiology; D044944:Acyl-CoA Dehydrogenases; D002247:Carbon Isotopes / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D005798:Genes, Bacterial; D007532:Isoleucine / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008985:Monensin / Q000096:biosynthesis / Q000378:metabolism; D010088:Oxidoreductases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics / Q000254:growth & development; D013379:Substrate Specificity; D014633:Valine / Q000378:metabolism
D000214:Acyl Coenzyme A; D002247:Carbon Isotopes; D007532:Isoleucine; C015357:methylmalonyl-coenzyme A; C024343:butyryl-coenzyme A; D008985:Monensin; D010088:Oxidoreductases; D044944:Acyl-CoA Dehydrogenases; C100154:acyl-CoA dehydrogenase (NADP+); D007930:Leucine; D014633:Valine; D019342:Acetic Acid