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Effects of enhanced lysine ε-aminotransferase activity on cephamycin biosynthesis in Streptomyces clavuligerus

  • Applied Microbial and Cell Physiology
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Abstract

A recombinant strain of S. clavuligerus (LHM100) that contains an additional copy of the gene (lat) encoding lysine ε-aminotransferase (LAT) was analyzed and compared to the wild-type for intracellular concentrations of primary metabolites involved in cephamycin C biosynthesis. This strain had been shown previously to produce higher levels of the antibiotic because of increased levels of LAT, a rate-limiting enzyme involved in the production of α-amino-adipic acid. The results showed that the overall growth kinetics of the two strains were comparable, including the intracellular concentrations of cysteine, valine and lysine. In contrast, 60% higher antibiotic production was observed in LHM100, which reflected a significant temporal variation in specific metabolite production rate. The time profile of LAT activity was consistently higher in LHM100; however, α-aminoadipic acid levels showed unexpected variation during the growth cycle. These results support the proposal that rate-limiting enzymes in cephamycin C biosynthesis are temporally controlled, and indicate that optimization of metabolite production will require differential overexpression of several biosynthetic genes.

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Authors and Affiliations

  1. Department of Chemical Engineering and Material Sciences, University of Minnesota, 55455, Minneapolis, Minnesota, USA

    L. -H. Malmberg & W. -S. Hu

  2. Department of Microbiology and Biological Process Technology Institute, University of Minnesota, 1479 Gortner Avenue, #240, 55108, St. Paul, Minnesota, USA

    D. H. Sherman

Authors
  1. L. -H. Malmberg
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  2. W. -S. Hu
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  3. D. H. Sherman
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Malmberg, L.H., Hu, W.S. & Sherman, D.H. Effects of enhanced lysine ε-aminotransferase activity on cephamycin biosynthesis in Streptomyces clavuligerus . Appl Microbiol Biotechnol 44, 198–205 (1995). https://doi.org/10.1007/BF00164502

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  • DOI: https://doi.org/10.1007/BF00164502

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