Patent ID: 7998732

Claim:
A process for production of plasmid DNA comprising: (a) selecting a highly productive clonal subtype of a strain of E. coli transformed with a DNA plasmid comprising: (i) observing a phenotypic heterogeneity in a population of colonies generated by the transformed E. coli , and selecting as potentially highly productive clonal subtypes those colonies that represent a minor component of said phenotypic heterogeneity in said population of colonies; (ii) purifying said potentially highly productive clonal subtypes and determining the productivity of said purified, potentially highly productive clonal subtypes by measuring the plasmid copy number per cell; and, (iii) selecting as a highly productive clonal subtype a potentially highly productive clonal subtype that exhibits a higher plasmid copy number per cell in comparison to non-selected, transformed E. coli clonal subtypes of the same strain; and, (b) cultivating said highly productive clonal subtype with fed-batch fermentation in chemically-defined medium in a fermentation volume of greater than 1000 L, wherein said phenotypic heterogeneity is observed after the transformed E. coli is grown on blood agar at about 30° C., and wherein the potentially highly productive clonal subtypes that represent the minor component of said phenotypic heterogeneity are gray colored-colonies while the major component of said phenotypic heterogeneity are white-colored colonies.