IMPROVEMENT OF ANTIBIOTIC TITERS FROM STREPTOMYCES BACTERIA BY INTERACTIVE CONTINUOUS SELECTION

We have applied a technique of interactive continuous selection (ICS) to the isolation of streptomycin-resistant mutants of the streptomycin -producing organism, Streptomyces griseus. A series of mutants, each w ith a different colonial morphology and expressing successively greate r resistance to streptomycin, was isolated during the course of select ion. Takeover of the mutants has been correlated with changes in on-li ne estimates of streptomycin concentration such that these estimates m ay be used as a real-time measure of the genetic state of the cell pop ulation. When grown in the medium employed for ICS, mutants expressed increased antibiotic production titers; the best mutant produced 10 to 20 times more streptomycin than the parent strain. Absolute improveme nts in the maximum specific growth rate and intrinsic resistance to st reptomycin did not account for the observed growth advantage of all mu tants. Rather, each mutant exhibited relative increases in specific gr owth rate at increasing concentrations of streptomycin. (C) 1996 John Wiley & Sons, Inc.