Mutation and a high-throughput screening method for improving the production of Epothilones of Sorangium
- 24 July 2007
- journal article
- research article
- Published by Oxford University Press (OUP) in Journal of Industrial Microbiology & Biotechnology
- Vol. 34 (9), 615-623
- https://doi.org/10.1007/s10295-007-0236-2
Abstract
The epothilones are highly promising prospective anticancer agents that are produced by the myxobacterium Sorangium cellulosum. We mutated the epothilone producing S. cellulosum strain So0157-2 to improve the production of epothilones. For evaluation in high-throughput of a large number of mutants, we developed a simple microtiter method for primary screening. Using the classical UV-mutation method plus selection pressures, the production capacity was increased about 0.5∼2.5 times the starting strain. The mutants with higher production and different phenotypes were further subjected to recursive protoplast fusions and the fusants products were screened under multi-selection pressure. Furthermore, the production was greatly increased by the genome shuffling. For epothilone B, the production of one fusant was increased about 130 times compared to the starting strain, increasing from 0.8 mg l−1 to 104 mg l−1.Keywords
This publication has 33 references indexed in Scilit:
- Epothilones in the treatment of cancerExpert Opinion on Investigational Drugs, 2006
- Genetic improvement of processes yielding microbial productsFEMS Microbiology Reviews, 2006
- Heterologous production of the antifungal polyketide antibiotic soraphen A of Sorangium cellulosum So ce26 in Streptomyces lividansMicrobiology, 2004
- Genome Shuffling Improves Degradation of the Anthropogenic Pesticide Pentachlorophenol by Sphingobium chlorophenolicum ATCC 39723Applied and Environmental Microbiology, 2004
- Development of a mariner -Based Transposon for Use in Sorangium cellulosumApplied and Environmental Microbiology, 2003
- Genome shuffling leads to rapid phenotypic improvement in bacteriaNature, 2002
- Improvement of industry-applied rifamycin B-producing strain, Amycolatopsis mediterranei, by rational screening.The Journal of General and Applied Microbiology, 2002
- The 387 kb linear plasmid pPZG101 of Streptomyces rimosus and its interactions with the chromosomeMicrobiology, 1994
- Conversion of protoplasts of colistin-producing Bacillus colistinus to L-forms and bacillary forms.Agricultural and Biological Chemistry, 1985
- Regeneration of mycelial protoplasts from Lyophyllum shimeji.Agricultural and Biological Chemistry, 1984