Monday, November 9, 2009
P10

Use of Antibiotic Resistant Mutagenesis and Fed-batch Fermentation to Enhance the Production of Insecticidal Macrolides and Bioactivity by Streptomyces galbus AQ6047

Colleen S. Taylor1, Laura Lampa1, Magalie Guilhabert-Goya1, Jon Margolis2, Desmond Jimenez1, Jorge I. Jimenez1, and Hong Zhu3. (1) AgraQuest, 1540 Drew Ave., Davis, CA 95618, (2) Sr. Vice President of Research and Development, AgraQuest, 1540 Drew Ave., Davis, CA 95618, (3) Director of Fermentation and Formulation, AgraQuest, 1540 Drew Ave., Davis, CA 95618

Insects cause over 22 billion dollars of crop damage in the United States alone.  Many of the widely used insecticides are older neurotoxic compounds and there is a substantial need for new, safer chemistries.  AQ6047 is a proprietary strain of Streptomyces galbus that produces a group of closely related macrolides exhibiting insecticidal activity only against Lepidoptera (caterpillars). Our focus was to develop a commercially feasible fermentation process for the production of the insecticidal macrolides.  Strain improvement and fermentation optimization were employed to increase the productivity of the insectidal macrolides. Libraries of mutants resistant to individual antibiotics (Gentamicin, Rifampicin, Streptomycin, Paromomycin or Tobramycin) were screened for macrolide overproduction and insecticidal activity.  Fermentation media and growth conditions were optimized for maximum macrolide production and bioactivity at both shake flask and bioreactor scale. Optimum macrolide production was achieved utilizing a fed-batch process.  The combination of antibiotic resistant mutants and fed-batch fermentation process resulted in a 13-fold increase in macrolide production and a 35-fold increase in bioactivity. 

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