Overexpression of a pathway specific negative regulator enhances production of daunorubicin in bldA deficient Streptomyces peucetius ATCC 27952
| Autor: | Amit Kumar Chaudhary, Jae Kyung Sohng, Anil Shrestha, Hue Thi Nguyen, Tuoi Thi Le, Kwangkyoung Liou, Dipesh Dhakal, Anaya Raj Pokhrel |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Transcription Genetic Daunorubicin Regulator Gene Expression Biology Microbiology Streptomyces 03 medical and health sciences Bacterial Proteins Cytochrome P-450 Enzyme System Transcription (biology) medicine Codon Gene Chromatography High Pressure Liquid health care economics and organizations Regulator gene fungi biology.organism_classification Molecular biology humanities Anti-Bacterial Agents 030104 developmental biology Biochemistry Streptomyces peucetius Heterologous expression Metabolic Networks and Pathways medicine.drug |
| Zdroj: | Microbiological Research. 192:96-102 |
| ISSN: | 0944-5013 |
| Popis: | The dnrO gene is the first regulator to be activated in the daunorubicin (DNR) biosynthesis pathway of Streptomyces peucetius ATCC 27952. DnrO is known for its self-repression capability while it activates rest of the DNR biosynthesis pathway through cascades of regulatory events. S. peucetius was found to contain no functional copy of bldA-tRNA while a detailed examination of dnrO codons reveals the presence of TTA codon, which is rarely encoded by bldA-tRNA. Therefore, for evaluating the role of dnrO in DNR production, multiple engineered strains of S. peucetius were generated by heterologously expressing bldA, dnrO and combination of bldA and dnrO. Using these strains, the effects of heterologously expressed bldA and overexpressed dnrO were evaluated on pathway specific regulators, mycelial densities and production of DNR. The results showed that the transcription level of dnrO and master regulator dnrI, was found to be elevated in bldA containing strain in comparison to dnrO overexpressed strain. The bldA containing strain produces 45.7% higher DNR than bldA deficient wild type strain from culture broth with OD600 of 1.45 at 72 h. Heterologous expression of bldA–tRNA is accounted for increased transcription levels of the DNR pathway specific regulators and enhanced DNR production. |
| Databáze: | OpenAIRE |
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