Precursor Supply for Polyketide Biosynthesis: The Role of Crotonyl-CoA Reductase
✍ Scribed by Haibin Liu; Kevin A. Reynolds
- Publisher
- Elsevier Science
- Year
- 2001
- Tongue
- English
- Weight
- 252 KB
- Volume
- 3
- Category
- Article
- ISSN
- 1096-7176
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✦ Synopsis
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.