Mutation and a high-throughput screening method for improving the production of Epothilones of Sorangium.
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 approximately 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).
Gong
Guo-li
GL
State Key Libratory of Microbial Technology, College of Life Science, Shan Dong University, Jinan 250100, People's Republic of China.
Sun
Xin
X
Liu
Xin-li
XL
Hu
Wei
W
Cao
Wen-rui
WR
Liu
Hong
H
Liu
Wei-feng
WF
Li
Yue-zhong
YZ
D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D034261:Epothilones / Q000096:biosynthesis*; D004852:Epoxy Compounds / Q000378:metabolism*; D009154:Mutation; D009231:Myxococcales / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism* / Q000528:radiation effects
D000970:Antineoplastic Agents; D034261:Epothilones; D004852:Epoxy Compounds; C093788:epothilone B