Production of pikromycin using branched chain amino acid catabolism in Streptomyces venezuelae ATCC 15439
| Autor: | Eun Jung Kim, Jeong Sang Yi, Byung-Gee Kim, Minsuk Kim |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Streptomyces venezuelae Branched-chain amino acid Secondary Metabolism Bioengineering Hydroxylation Applied Microbiology and Biotechnology 03 medical and health sciences chemistry.chemical_compound Polyketide Mutase Methylmalonyl-CoA biology Acyl carrier protein synthase Catabolism biology.organism_classification Streptomyces Anti-Bacterial Agents 030104 developmental biology Biochemistry chemistry biology.protein Macrolides Pikromycin Amino Acids Branched-Chain Biotechnology |
| Zdroj: | Journal of industrial microbiologybiotechnology. 45(5) |
| ISSN: | 1476-5535 |
| Popis: | Branched chain amino acids (BCAA) are catabolized into various acyl-CoA compounds, which are key precursors used in polyketide productions. Because of that, BCAA catabolism needs fine tuning of flux balances for enhancing the production of polyketide antibiotics. To enhance BCAA catabolism for pikromycin production in Streptomyces venezuelae ATCC 15439, three key enzymes of BCAA catabolism, 3-ketoacyl acyl carrier protein synthase III, acyl-CoA dehydrogenase, and branched chain α-keto acid dehydrogenase (BCDH) were manipulated. BCDH overexpression in the wild type strain resulted in 1.3 fold increase in pikromycin production compared to that of WT, resulting in total 25 mg/L of pikromycin. To further increase pikromycin production, methylmalonyl-CoA mutase linked to succinyl-CoA production was overexpressed along with BCDH. Overexpression of the two enzymes resulted in the highest titer of total macrolide production of 43 mg/L, which was about 2.2 fold increase compared to that of the WT. However, it accumulated and produced dehydroxylated forms of pikromycin and methymycin, including their derivatives as well. It indicated that activities of pikC, P450 monooxygenase, newly became a bottleneck in pikromycin synthesis. |
| Databáze: | OpenAIRE |
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