Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.3.1.8 (acyl-CoA dehydrogenase)
 785 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ccr encoding crotonyl coenzyme A (CoA) reductase (CCR), which catalyzes the conversion of crotonyl-CoA to butyryl-CoA in the presence of NADPH, was previously cloned from Streptomyces collinus. We now report that a complete open reading frame, designated meaA, is located downstream from ccr. The predicted gene product showed 35% identity with methylmalonyl-CoA mutases from various sources. In addition, the predicted amino acid sequences of S. collinus ccr and meaA exhibit strong similarity to that of adhA (43% identity), a putative alcohol dehydrogenase gene, and meaA (62% identity) of Methylobacterium extorquens, respectively. Both adhA and meaA are involved in the assimilation of C1 and C2 compounds in an unknown pathway in the isocitrate lyase (ICL)-negative Methylobacterium. We have demonstrated that S. collinus can grow with acetate as its sole carbon source even though there is no detectable ICL, suggesting that in this organism ccr and meaA may also be involved in a pathway for the assimilation of C2 compounds. Previous studies with streptomycetes provided a precedent for a pathway that initiates with the condensation of two acetyl-CoA molecules to form butyryl-CoA, which is then transformed to succinyl-CoA with two separate CoB12-mediated rearrangements and a series of oxidations. The biological functions of ccr and meaA in this process were investigated by gene disruption. A ccr-blocked mutant showed no detectable crotonyl-CoA reductase activity and, compared to the wild-type strain, exhibited dramatically reduced growth when acetate was the sole carbon source. An meaA-blocked mutant also exhibited reduced growth on acetate. However, both methylmalonyl-CoA mutase and isobutyryl-CoA mutase, which catalyze the two CoB12-dependent rearrangements in this proposed pathway, were shown to be present in the meaA-blocked mutant. These results suggested that both ccr and meaA are involved in a novel pathway for the growth of S. collinus when acetate is its sole carbon source.
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PMID:A novel alternate anaplerotic pathway to the glyoxylate cycle in streptomycetes. 926 Sep 59

Transcript levels in production cultures of wildtype and classically improved strains of the actinomycete bacteria Saccharopolyspora erythraea and Streptomyces fradiae were monitored using microarrays of the sequenced actinomycete S. coelicolor. Sac. erythraea and S. fradiae synthesize the polyketide antibiotics erythromycin and tylosin, respectively, and the classically improved strains contain unknown overproduction mutations. The Sac. erythraea overproducer was found to express the entire 56-kb erythromycin gene cluster several days longer than the wildtype strain. In contrast, the S. fradiae wildtype and overproducer strains expressed the 85-kb tylosin biosynthetic gene cluster similarly, while they expressed several tens of other S. fradiae genes and S. coelicolor homologs differently, including the acyl-CoA dehydrogenase gene aco and the S. coelicolor isobutyryl-CoA mutase homolog icmA. These observations indicated that overproduction mechanisms in classically improved strains can affect both the timing and rate of antibiotic synthesis, and alter the regulation of antibiotic biosynthetic enzymes and enzymes involved in precursor metabolism.
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PMID:Reverse engineering of industrial pharmaceutical-producing actinomycete strains using DNA microarrays. 1525 8