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Cephalosporins

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Biosynthesis and Molecular Genetics of Fungal Secondary Metabolites

Part of the book series: Fungal Biology ((FUNGBIO))

Abstract

Cephalosporin C is a β-lactam antibiotic with antibacterial activity against both Gram-positive and Gram-negative bacteria. This pharmaceutically important drug is produced by the filamentous fungus Acremonium chrysogenum, which is used in industrial applications worldwide. Here we summarize the fungal biosynthetic pathway that leads to the production of the secondary metabolite cephalosporin C and its intermediates. Chemical derivatives of intermediates of this pathway show elevated antibiotic activity, and are used in medical applications. A. chrysogenum exhibits a rather slow growth rate and peculiar hyphal morphology, which hamper its manipulation by genetic engineering. We present a concise overview of the recently developed novel molecular tools for use with A. chrysogenum, and we describe methods for increasing efficiencies of targeted strain improvements. Genetic analyses have identified several transcription factors, transporters, and other regulators that are involved in both cephalosporin C biosynthesis and fungal morphology. Despite strong progress, our understanding of the regulatory mechanisms controlling cephalosporin C biosynthesis remains incomplete. Future work must therefore focus on the application of advanced genetic techniques. Together with the awaited genome sequence data, such studies will elucidate the molecular mechanisms underlying A. chrysogenum physiology and morphology.

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Notes

  1. 1.

    D. Löper and U. Kück, unpublished.

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Acknowledgements

The experimental work of the authors is funded by the Christian Doppler Society (Vienna) and Sandoz GmbH (Kundl). We are deeply thankful to Gabriele Frenßen-Schenkel for the artwork, and to MSc Janina Kluge and MSc Dominik Terfehr for their help with some figures. We further thank Isabel van der Kamp for her support in preparing the chapter about cephalosporin derivatives.

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Authors and Affiliations

  1. Christian Doppler Laboratory for Fungal Biotechnology, Lehrstuhl für Allgemeine und Molekulare Botanik, Ruhr-Universität Bochum, Bochum, Germany

    Sandra Bloemendal & Ulrich Kück

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  1. Sandra Bloemendal
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  2. Ulrich Kück
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Correspondence to Ulrich Kück .

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Editors and Affiliations

  1. Department of Molecular Biology, University of León, León, Spain

    Juan-Francisco Martín

  2. Parque Científico de León, Instituto de Biotecnología de León (INBIOTEC), León, Spain

    Carlos García-Estrada

  3. Institute of Chemical Engineering, Vienna University of Technology, Vienna, Austria

    Susanne Zeilinger

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Bloemendal, S., Kück, U. (2014). Cephalosporins. In: Martín, JF., García-Estrada, C., Zeilinger, S. (eds) Biosynthesis and Molecular Genetics of Fungal Secondary Metabolites. Fungal Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1191-2_3

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