期刊
METABOLIC ENGINEERING
卷 6, 期 4, 页码 313-325出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ymben.2004.04.001
关键词
metabolic flux analysis; CDA; Streptomyces coelicolor; nonribosomal peptide synthetases; in silico; mutasynthesis
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 metabolism of S. coelicolor and used computational metabolic flux balancing to investigate some of the factors affecting growth and production of CDA. Computational results indicated that the CDA production was concomitant with growth. Computational specific growth rates were twice as high as the experimental specific growth rates. Metabolic flux distributions and sensitivity analyses computed for various phases of the batch culture indicated that the specific CDA production 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 production rate. (C) 2004 Elsevier Inc. All rights reserved.
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