Saccharopolyspora erythraea-catalyzed bioconversion of 6-deoxyerythronolide B analogs for production of novel erythromycins
| Autor: | Sajel Patel, Sally Ou, Christopher Carreras, Peter J. Licari, Timothy Leaf, Scott Frykman, Lawrence Cadapan, Elaine Woo, Gary W. Ashley, John R. Carney, Mark A. Burlingame, Stefan Zavala |
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| Rok vydání: | 2002 |
| Předmět: |
Bioconversion
Stereochemistry Bioengineering Applied Microbiology and Biotechnology Streptomyces Polyketide chemistry.chemical_compound Bioreactors Multienzyme Complexes Polyketide synthase Biotransformation Molecular Structure biology Streptomyces coelicolor General Medicine biology.organism_classification Culture Media Erythromycin Saccharopolyspora Kinetics Aglycone chemistry Mutation biology.protein Saccharopolyspora erythraea Plasmids Biotechnology |
| Zdroj: | Journal of Biotechnology. 92:217-228 |
| ISSN: | 0168-1656 |
| Popis: | A method was developed for the large-scale bioconversion of novel 6-deoxyerythronolide B (6-dEB) analogs into erythromycin analogs. Erythromycin biosynthesis in Saccharopolyspora erythraea proceeds via the formation of a polyketide aglycone, 6-dEB, which is subsequently glycosylated, hydroxylated and methylated to yield the antibiotic erythromycin A. A modular polyketide synthase (PKS) directs 6-dEB synthesis using a dedicated set of active sites for the condensation of each of seven propionate units. Strategies based on genetic manipulation and precursor feeding are available for the efficient generation of novel 6-dEB analogs using a plasmid-based system in Streptomyces coelicolor. 6-dEB and 13-substituted 6-dEB analogs produced in this manner were fed to S. erythraea mutants which could not produce 6-dEB, yet retained their 6-dEB modification systems, and resulted in the generation of erythromycin A and 13-substituted erythromycin A analogs. Erythromycin B, C and D analogs were observed as intermediates of the process. Dissolved oxygen, temperature, the specific aglycone feed concentration, and pH were found to be important for obtaining a high yield of erythromycin A analogs. Cultivation conditions were identified which resulted in the efficient bioconversion of 6-dEB analogs into erythromycin A analogs, which this process demonstrated at the 100 l scale. |
| Databáze: | OpenAIRE |
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