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

L. H. Malmberg, W. S. Hu, D. H. Sherman

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28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)198-205
Number of pages8
JournalApplied Microbiology and Biotechnology
Volume44
Issue number1-2
DOIs
StatePublished - Dec 1995

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