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Metabolic flux analysis for calcium dependent antibiotic (CDA) production in Streptomyces coelicolor.
H. B. Kim, C. P. Smith, J. Micklefield and F. Mavituna*
Metabolic Engineering. 2004;6:313-325.
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Abstract
The calcium dependent antibiotic (CDA) is a nonribosomal lipopeptide produced by Streptomyces coelicolor. We constructed a metabolic network of more than 400 reactions for the primary and secondary metab. of S. coelicolor and used computational metabolic flux balancing to investigate some of the factors affecting growth and prodn. of CDA. Computational results indicated that the CDA prodn. was concomitant with growth. Computational specific growth rates were twice as high as the exptl. specific growth rates. Metabolic flux distributions and sensitivity analyses computed for various phases of the batch culture indicated that the specific CDA prodn. rate was affected by nitrogen assimilation, pentose phosphate pathway, shikimate biosynthesis, and oxoglutarate fluxes. Consequently, these metabolic targets were tested using genetic deletions in the model which increased the in silico specific CDA prodn. rate. [on SciFinder (R)]
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