FED-BATCH FERMENTATION PROCESS AND CULTURE MEDIUM FOR PRODUCTION OF PLASMID DNA IN E. COLI IN MANUFACTURING SCALE

摘要

PPROBLEM TO BE SOLVED: To provide a method for producing high homogeneity plasmid DNA in high yield. PSOLUTION: The method for producing plasmid DNA in a manufacturing scale, wherein E. coli cells having a plasmid are grown in a pre-culture and subsequently fermented in a main culture, recovered and purified the product plasmid DNA, the main culture is a fed-batch process comprising a batch phase and a nutrient feeding phase, wherein (a) the culture medium of the batch phase and the nutrient feeding phase are chemically defined, and (b) the medium in the nutrient feeding phase maintains a predetermined relative proliferation rate by comprising that (i) the culture medium of the nutrient feeding phase comprises a growth-limiting substrate and (ii) the culture medium is added at a feeding rate that follows, for at least a fraction of the feeding phase, a pre-defined exponential function. PCOPYRIGHT: (C)2011,JPO&INPIT