Crotonyl-coenzyme A reductase provides methylmalonyl-CoA precursors for monensin biosynthesis by Streptomyces cinnamonensis in an oil-based extended fermentation

Li, C.

doi:10.1099/mic.0.27251-0

Cited by 32 publications

(40 citation statements)

References 48 publications

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“…In Streptomyces, methylmalonyl-CoA and ethylmalonylCoA are two of the most common chain extender units for the biosynthesis of many polyketide antibiotics, and several pathways for their generation have been proposed (Hopwood & Sherman, 1990;Zhang & Reynolds, 2001 (Birch et al, 1993;Li et al, 2004). In addition, a meaA gene, which shares similarity with the large subunit of methylmalonyl-CoA mutase, was involved in an unknown pathway to methylmalonyl-CoA formation (Zhang & Reynolds, 2001).…”

Section: Orthologous Phx Genes In Two Streptomyces Genomesmentioning

confidence: 99%

Predicted highly expressed genes in the genomes of Streptomyces coelicolor and Streptomyces avermitilis and the implications for their metabolism

2005

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Highly expressed genes in bacteria often have a stronger codon bias than genes expressed at lower levels, due to translational selection. In this study, a comparative analysis of predicted highly expressed (PHX) genes in the Streptomyces coelicolor and Streptomyces avermitilis genomes was performed using the codon adaptation index (CAI) as a numerical estimator of gene expression level. Although it has been suggested that there is little heterogeneity in codon usage in G+C-rich bacteria, considerable heterogeneity was found among genes in these two G+C-rich Streptomyces genomes. Using ribosomal protein genes as references,~10 % of the genes were predicted to be PHX genes using a CAI cutoff value of greater than 0?78 and 0?75 in S. coelicolor and S. avermitilis, respectively. The PHX genes showed good agreement with the experimental data on expression levels obtained from proteomic analysis by previous workers. Among 724 and 730 PHX genes identified from S. coelicolor and S. avermitilis, 368 are orthologue genes present in both genomes, which were mostly 'housekeeping' genes involved in cell growth. In addition, 61 orthologous gene pairs with unknown functions were identified as PHX. Only one polyketide synthase gene from each Streptomyces genome was predicted as PHX. Nevertheless, several key genes responsible for producing precursors for secondary metabolites, such as crotonyl-CoA reductase and propionyl-CoA carboxylase, and genes necessary for initiation of secondary metabolism, such as adenosylmethionine synthetase, were among the PHX genes in the two Streptomyces species. The PHX genes exclusive to each genome, and what they imply regarding cellular metabolism, are also discussed.

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Section: Orthologous Phx Genes In Two Streptomyces Genomesmentioning

confidence: 99%

Predicted highly expressed genes in the genomes of Streptomyces coelicolor and Streptomyces avermitilis and the implications for their metabolism

2005

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“…This observation suggested that under these growth conditions the butyryl-CoA pathway was important for providing ethylmalonyl-CoA (formed by carboxylation of butyryl-CoA) for monensin A biosynthesis, but not in methylmalonyl-CoA. More recently it has been shown that in an oil-based extended fermentation medium, there is a dramatic decrease in the methylmalonyl-CoA pool and overall titers for the L1 mutant as compared to the parent strain [11]. This observation indicates that under these conditions where the major carbon source comes from lipid degradation and enters central metabolism at the level of acetyl-CoA, the butyryl-CoA pathway provides the major route to methylmalonylCoA.…”

Section: Introductionmentioning

confidence: 93%

Multiple pathways for acetate assimilation in Streptomyces cinnamonensis

Akopiants

Florova

et al. 2005

J IND MICROBIOL BIOTECHNOL

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In most bacteria acetate assimilation is accomplished via the glyoxylate pathway. Isocitrate lyase (ICL) and malate synthase (MS) are two key enzymes of this pathway, which results in the net generation of one molecule of succinyl-CoA from two acetyl-CoA molecules. Genetic and biochemical data have shown that genes encoding these key enzymes are present in streptomycetes, yet there has been no clear demonstration of the importance of these genes to acetate assimilation. In fact, for Streptomyces collinus an alternative butyryl-CoA pathway has been shown to be critical for growth on acetate as a sole carbon source. Crotonyl-CoA reductase (CCR) is a key enzyme in this pathway and catalyzes the last step of the conversion of 2-acetyl-CoA molecules to butyryl-CoA. In Streptomyces cinnamonensis C730.1, it has been shown that CCR and this butyryl-CoA pathway provide the majority of methylmalonyl-CoA and ethylmalonyl-CoA for monensin A biosynthesis in an oil-based fermentation medium. We have cloned a MS homologue gene from this strain. Reverse transcription and direct enzyme assays demonstrated that neither this nor other MS genes were expressed during fermentation in an oil-based fermentation of either the C730.1 or L1 strain (a ccr mutant). Similarly, no ICL activity could be detected. The C730.1 but not the L1 strain was able to grow on acetate as a sole carbon source. The Streptomyces coelicolor aceA and aceB2 genes encoding ICL and MS were cloned into a Streptomyces expression plasmid (a derivative of pSET152) to create pExIM1. Enzyme assays and transcript analyses demonstrated expression of both of these proteins in C730.1/pExIM1 and L1/pExIM1 grown in an oil-based fermentation and tryptic soy broth media. Nonetheless, L1/pExIM1, like L1, was unable to grow on acetate as a sole carbon source, and was unable to efficiently generate precursors for monensin A biosynthesis in an oil-based fermentation, indicating that the additional presence of these two enzyme activities does not permit a functional glyoxylate cycle to occur. UV mutagenesis of S. cinnamonensis L1 and L1/pExIM1 led to mutants which were able to grow efficiently on acetate despite a block in the butyryl-CoA pathway. Analysis of enzyme activity and monensin production from these mutants in an oil-based fermentation demonstrated that neither the glyoxylate cycle nor the butyryl-CoA pathway function, suggesting the possibility of alternative pathways of acetate assimilation.

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“…Furthermore, there may be lower levels of other naturally occurring acylated PLM products which have not yet been identified from these strains. These PLMs may be generated by PlmS 3 -catalyzed acylation of PLM G with other branched-chain acyl-CoAs or straight-chain acyl-CoA substrates (butyryl-CoA and crotonyl-CoA are both known primary metabolites [16] and substrates for this enzyme).…”

Section: Discussionmentioning

confidence: 99%

Application of a Newly Identified and Characterized 18- O -Acyltransferase in Chemoenzymatic Synthesis of Selected Natural and Nonnatural Bioactive Derivatives of Phoslactomycins

Ghatge

Palaniappan

Alhamadsheh

et al. 2009

Appl Environ Microbiol

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Crotonyl-coenzyme A reductase provides methylmalonyl-CoA precursors for monensin biosynthesis by Streptomyces cinnamonensis in an oil-based extended fermentation

Cited by 32 publications

References 48 publications

Predicted highly expressed genes in the genomes of Streptomyces coelicolor and Streptomyces avermitilis and the implications for their metabolism

Predicted highly expressed genes in the genomes of Streptomyces coelicolor and Streptomyces avermitilis and the implications for their metabolism

Multiple pathways for acetate assimilation in Streptomyces cinnamonensis

Application of a Newly Identified and Characterized 18- O -Acyltransferase in Chemoenzymatic Synthesis of Selected Natural and Nonnatural Bioactive Derivatives of Phoslactomycins

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