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Lysine biosynthesis in microbes: relevance as drug target and prospects for β-lactam antibiotics production

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Abstract

Plants as well as pro- and eukaryotic microorganisms are able to synthesise lysine via de novo synthesis. While plants and bacteria, with some exceptions, rely on variations of the meso-diaminopimelate pathway for lysine biosynthesis, fungi exclusively use the α-aminoadipate pathway. Although bacteria and fungi are, in principle, both suitable as lysine producers, current industrial fermentations rely on the use of bacteria. In contrast, fungi are important producers of β-lactam antibiotics such as penicillins or cephalosporins. The synthesis of these antibiotics strictly depends on α-aminoadipate deriving from lysine biosynthesis. Interestingly, despite the resulting industrial importance of the fungal α-aminoadipate pathway, biochemical reactions leading to α-aminoadipate formation have only been studied on a limited number of fungal species. In this respect, just recently an essential isomerisation reaction required for the formation of α-aminoadipate has been elucidated in detail. This review summarises biochemical pathways leading to lysine production, discusses the suitability of interrupting lysine biosynthesis as target for new antibacterial and antifungal compounds and emphasises on biochemical reactions involved in the formation of α-aminoadipate in fungi as an essential intermediate for both, lysine and β-lactam antibiotics production.

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Acknowledgements

Work of MB is supported by grants from the German Science foundation (DFG), the Jena School for Microbial Communication (JSMC) and funds from the Hans-Knoell-Institute (HKI). The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Microbial Biochemistry and Physiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Beutenbergstr. 11a, 07745, Jena, Germany

    Felicitas Fazius & Matthias Brock

  2. Biomolecular Chemistry, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute, Beutenbergstr. 11a, 07745, Jena, Germany

    Christoph Zaehle

  3. Department for Microbiology and Molecular Biology, Institute for Microbiology, Friedrich-Schiller University Jena, Jena, Germany

    Matthias Brock

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  1. Felicitas Fazius
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  2. Christoph Zaehle
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Correspondence to Matthias Brock.

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Fazius, F., Zaehle, C. & Brock, M. Lysine biosynthesis in microbes: relevance as drug target and prospects for β-lactam antibiotics production. Appl Microbiol Biotechnol 97, 3763–3772 (2013). https://doi.org/10.1007/s00253-013-4805-1

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