Direct production of ivermectin-like drugs after domain exchange in the avermectin polyketide synthase of Streptomyces avermitilis ATCC31272
| Autor: | Barrie Wilkinson, Steven G. Kendrew, Lindsey Low, Rose Mary Sheridan, James Staunton, Rachel E. Lill, Peter F. Leadlay, Alison J. Weston, Ian S. Galloway, Gabriele Wirtz, Sabine Gaisser, Kim Jonelle Stutzman-Engwall, Hamish A. I. McArthur, Andrew L. Kaja, Laurenz Kellenberger |
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| Rok vydání: | 2003 |
| Předmět: |
Biochemistry
Microbiology Polyketide chemistry.chemical_compound Ivermectin Multienzyme Complexes Polyketide synthase medicine Physical and Theoretical Chemistry Avermectin biology Organic Chemistry biology.organism_classification medicine.disease Antiparasitic agent Streptomyces Protein Structure Tertiary Blotting Southern chemistry Genes Bacterial Drug Design Fermentation Mutation biology.protein Onchocerciasis Streptomyces avermitilis Bacteria medicine.drug |
| Zdroj: | Organicbiomolecular chemistry. 1(16) |
| ISSN: | 1477-0520 |
| Popis: | Ivermectin™, a mixture of 22,23-dihydroavermectin B1a 9 with minor amounts of 22,23-dihydroavermectin B1b 10, is one of the most successful veterinary antiparasitic drugs ever produced. In humans, ivermectin has been used for the treatment of African river blindness (onchocerciasis) resulting in an encouraging decrease in the prevalence of skin and eye diseases linked to this infection. The components of ivermectin are currently synthesized by chemical hydrogenation of a specific double bond at C22–C23 in the polyketide macrolides avermectins B1a 5 and B1b 6, broad-spectrum antiparasitic agents isolated from the soil bacterium Streptomyces avermitilis. We describe here the production of such compounds (22,23-dihydroavermectins B1a 9 and A1a 11) by direct fermentation of a recombinant strain of S. avermitilis containing an appropriately-engineered polyketide synthase (PKS). This suggests the feasibility of a direct biological route to this valuable drug. |
| Databáze: | OpenAIRE |
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