Antonie van Leeuwenhoek

, Volume 64, Issue 2, pp 145–163 | Cite as

Molecular aspects of lysine, threonine, and isoleucine biosynthesis inCorynebacterium glutamicum

  • Bernhard J. Eikmanns
  • Lothar Eggeling
  • Hermann Sahm


The Gram-positive bacteriumCorynebactericum glutamicum is used for the industrial production of amino acids, e.g. of L-glutamate and L-lysine. In the last ten years genetic engineering methods were developed forC. glutamicum and consequently, recombinant DNA technology was employed to study the biosynthetic pathways and to improve the amino acid productivity by manipulation of enzymatic, transport and regulatory functions of this bacterium. The present review summarizes the current knowledge on the synthesis and over-production of the aspartate derived amino acids L-lysine, L-threonine and L-isoleucine inC. glutamicum. A special feature ofC. glutamicum is its abilily to convert the lysine intermediate piperideine2,6-dicarboxylate to diaminopimelate by two different routes, i.e. by reactions involving succinylated intermediates or by the single reaction of diaminopimelate dehydrogenase. The flux distribution over the two pathways is regulated by the ammonium availability. The overall carbon flux from aspartate to lysine, however, is governed by feedback-control of the aspartate kinase and by the level of dihydrodipicolinate synthase. Consequently, expression oflysCFBR encoding a deregulated aspartate kinase and/or the overexpression ofdapA encoding dihydrodipicolinate synthase led to overproduction of lysine. As a further specific featureC. glutamicum possesses a specific lysine export carrier which shows high activity in lysine overproducing mutants. Threonine biosynthesis is in addition to control by the aspartate kinase tightly regulated at the level of homoserine dehydrogenase which is subject to feedback-inhibition and to repression.C. glutamicum strains possessing a deregulated aspartate kinase and a deregulated homoserine dehydrogenase produce lysine and threonine. Amplification of deregulated homoserine dehydrogenase in such strain led to an almost complete redirection of the carbon flux to threonine. For a further flux from threonine to isoleucine the allosteric control of threonine dehydratase and of the acetohydroxy acid synthase are important. The expression of the genes encoding the latter enzyme is additionally regulated at the transcriptional level. By addition of 2-oxobutyrate as precursor and by bypassing the expression control of the acetohydroxy acid synthase genes high isoleucine overproduction can be obtained.

Key words

isolecucine biosynthesis lysine threonine 


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Copyright information

© Kluwer Academic Publishers 1993

Authors and Affiliations

  • Bernhard J. Eikmanns
    • 1
  • Lothar Eggeling
    • 1
  • Hermann Sahm
    • 1
  1. 1.Forschungszentrum Jülich GmbHInstitut für BiotechnologieJülichGermany

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