Branched-chain amino acid catabolism provides precursors for the Type II polyketide antibiotic, actinorhodin, via pathways that are nutrient dependent
| Autor: | Janet Westpheling, Karen Stirrett, Claudio D. Denoya |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Stereochemistry
Branched-chain amino acid Anthraquinones Streptomyces coelicolor Bioengineering Applied Microbiology and Biotechnology Actinorhodin Polyketide chemistry.chemical_compound Bacterial Proteins Valine chemistry.chemical_classification biology Catabolism biology.organism_classification Anti-Bacterial Agents Biosynthetic Pathways Amino acid Acyl carrier protein chemistry Biochemistry biology.protein Macrolides Amino Acids Branched-Chain Biotechnology |
| Zdroj: | Journal of Industrial Microbiology & Biotechnology. 36:129-137 |
| ISSN: | 1476-5535 1367-5435 |
| DOI: | 10.1007/s10295-008-0480-0 |
| Popis: | Polyketide antibiotics are among the most important therapeutics used in human and animal health care. Type II polyketides are composed primarily of acetate-derived thioesters, and the subunits for the PKS are contained in a single module that includes a ketosynthase, acyl carrier protein, chain-length factor and sometimes a keto-reductase, aromatase, cyclase and modifying enzymes, such as glycosylases or hydroxylases. While the enzyme complexes that make up the PKS have been the focus of intense study (Khosla in Chem Rev 7:2577-2590, 1997), the pathways for precursor synthesis have not been established and predictions are complicated by the fact that acetate may be derived from a number of metabolic pathways. Here we show that 50% of the acetate for synthesis of the Type II polyketide, actinorhodin, in Streptomyces coelicolor, is derived from the catabolism of the branched amino acids by pathways that are nutrient dependent. The streptomycetes are apparently unique in that they contain two BCDH gene clusters, each of which is potentially capable of converting leucine, valine and isoleucine to the corresponding thioesters, and contain at least three different pathways for valine catabolism that are differentially used in response to nutrient availability. |
| Databáze: | OpenAIRE |
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