Improvement of sordarin production through process optimization: combining traditional approaches with DOE.
BMS-353645, also known as sordarin, was of interest based on its activity against pathogenic fungi. The objective of these studies was to provide high quality starting substrate for chemical modification aimed at further improving biological activity, with particular interest in the inhibition of Aspergillus. In the work presented here, Design of Experiments, or DOE, was successfully combined with traditional approaches to significantly improve sordarin yields in fermentation flasks. Overall, yields were increased 25-fold from <100 microg/g to as high as 2,609 microg/g in flasks through the use of various medium and conduction changes supplemented with DOE. The improved process was then successfully scaled to pilot plant tanks with the best batch producing 2,389 microg/g sordarin at the 250-l scale.
Tully
Thomas P
TP
Enzyme Technology, Process Research and Development, Bristol-Myers Squibb Pharmaceutical Research Institute, P. O. Box 191, New Brunswick, NJ 08903, USA. thomas.tully@bms.com
Bergum
James S
JS
Schwarz
Steven R
SR
Durand
Susan C
SC
Howell
Jeffrey M
JM
Patel
Ramesh N
RN
Cino
Paul M
PM
D005285:Fermentation; D007192:Indenes / Q000378:metabolism*; D012107:Research Design; D020037:Sordariales / Q000378:metabolism*
D007192:Indenes; C003329:sordarin