Enhanced production of heterologous macrolide aglycones by fed-batch cultivation of Streptomyces coelicolor |
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Authors: | R P Desai T Leaf E Woo P Licari |
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Institution: | (1) Department of Process Science, Kosan Biosciences, Inc., 3832 Bay Center Place, Hayward, CA 94545, USA, US |
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Abstract: | A media development program for the enhanced production of macrolide aglycones by Streptomyces coelicolor is described. Shake flask studies utilizing a yeast extract and a bakers' yeast increased production by 200% and 80%, respectively.
However, ammonia generation and high pH were identified as potential problems in these enriched media. Studies in pH-controlled
fermentors revealed that production stage pH significantly affects macrolide titers, with low pH (5.5) being more productive
than high pH (6.5). Implementation of glucose feeding in shake flask cultures reduced ammonia generation and controlled production
stage pH, resulting in significantly enhanced productivities. The combined effects of media supplementation and glucose feeding
resulted in a three to five-fold overall improvement in total macrolide aglycone titers, and is the first reported high-level
(>1 g/l) production of recombinant polyketides in a heterologous host. Journal of Industrial Microbiology & Biotechnology (2002) 28, 297–301 DOI: 10.1038/sj/jim/7000246
Received 06 August 2001/ Accepted in revised form 26 January 2002 |
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Keywords: | : media development macrolide aglycones S coelicolor fed-batch cultivations |
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