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Use of soybean oil and ammonium sulfate additions to optimize secondary metabolite production

✍ Scribed by B. Junker; Z. Mann; P. Gailliot; K. Byrne; J. Wilson


Publisher
John Wiley and Sons
Year
1998
Tongue
English
Weight
178 KB
Volume
60
Category
Article
ISSN
0006-3592

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✦ Synopsis


A valine-overproducing mutant (MA7040, Streptomyces hygroscopicus) was found to produce 1.5 to 2.0 g/L of the immunoregulant, L-683,590, at the 0.6 m 3 fermentation scale in a simple batch process using soybean oil and ammonium sulfate-based GYG5 medium. Levels of both lower (L-683,795) and higher (HH1 and HH2) undesirable homolog levels were controlled adequately. This batch process was utilized to produce broth economically at the 19 m 3 fermentation scale. Material of acceptable purity was obtained without the multiple pure crystallizations previously required for an earlier culture, MA6678, requiring valine supplementation for impurity control.

Investigations at the 0.6 m 3 fermentation scale were conducted, varying agitation, pH, initial soybean oil/ ammonium sulfate charges, and initial aeration rate to further improve growth and productivity. Mid-cycle ammonia levels and lipase activity appeared to have an important role. Using mid-cycle soybean oil additions, a titer of 2.3 g/L of L-683,590 was obtained, while titers reached 2.7 g/L using mid-cycle soybean oil and ammonium sulfate additions. Both higher and lower homolog levels remained acceptable during this fed-batch process. Optimal timing of mid-cycle oil and ammonium sulfate additions was considered a critical factor to further titer improvements.