Wednesday, November 11, 2009 - 8:00 AM
S31

Fifty Years of Exploring for Improved Strains without a Map

Richard DeMaio1, Dale Brown2, Richard Copeland3, Lac Nguyen4, Robert Strobel2, and William Vassiliou3. (1) Research Advisor, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, IN 46085, (2) Research Scientist, Eli Lilly & Co., Indianapolis, IN 46285, (3) Associate Consultant Scientist, Eli Lilly & Co., Clinton, IN 47842, (4) Consultant Scientist, Eli Lilly & Co., Indianapolis, IN 46285

For over fifty years, Eli Lilly and Company has been successful in selecting improved strains and improving the fermentation efficiency of its Natural Product producing process.  The strategy used to attain these gains relies on the integration of three distinct improvement programs:  1) strain improvement through random chemical mutation, 2) strain scale-up and optimization in Pilot Plant bioreactors and 3) effective implementation and monitoring at full production scale.  While recent advances in molecular biology and proteonomics have improved our understanding of the Natural Product biosynthetic pathways and their regulation, Lilly continues to rely on an efficient high-throughput classical strain improvement program to generate improved strains.  Strains identified in the lab are then passed to the second leg of the improvement triad, the Pilot Plant, for confirmation and scale-up.  The Pilot Plant, however, is not merely a hurdle for strains to clear on the road to production; it also evaluates and generates novel process changes for implementation.   The final leg of our improvement strategy (full scale production) relies on the effective and rapid implementation of the strains discovered in the lab and innovations developed in the Pilot Plant.  As with the Pilot Plant, the production technical staff plays an important role in developing improvements through data mining and "listening" to the fermentation process to generate improvements for further investigation.  In total, good basic science, understanding of fermentation models (at a variety of scales) and effective bioengineering are used to maintain an effective improvement program.

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