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Compartmentalization and Transport in β-Lactam Antibiotics Biosynthesis

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Classical strain improvement of β-lactam producing organisms by random mutagenesis has been a powerful tool during the last century. Current insights in the biochemistry and genetics of β-lactam production, in particular in the filamentous fungus Penicillium chrysogenum, however, make a more directed and rational approach of metabolic pathway engineering possible. Besides the need for efficient genetic methods, a thorough understanding is needed of the metabolic fluxes in primary, intermediary and secondary metabolism. Controlling metabolic fluxes can be achieved by adjusting enzyme activities and metabolite levels in such a way that the main flow is directed towards the desired product. In addition, compartmentalization of specific parts of the β-lactam biosynthesis pathways provides a way to control this pathway by clustering enzymes with their substrates inside specific membrane bound structures sequestered from the cytosol. This compartmentalization also requires specific membrane transport steps of which the details are currently uncovered.

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1. Department of Molecular Microbiology & Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9751 NN, Kerklaan 30, Haren, The Netherlands

   M. E. Evers, H. Trip & A. J. M. Driessen

2. DSM Anti-infectives, 2611 XT, Delft, A. Fleminglaan 1, The Netherlands

   M. A. van den Berg & R. A. L. Bovenberg

1. M. E. Evers
2. H. Trip
3. M. A. van den Berg
4. R. A. L. Bovenberg
5. A. J. M. Driessen

Correspondence to A. J. M. Driessen .

A. A. Brakhage

Evers, M.E., Trip, H., van den Berg, M.A., Bovenberg, R.A.L., Driessen, A.J.M. Compartmentalization and Transport in β-Lactam Antibiotics Biosynthesis. In: Brakhage, A.A. (eds) Molecular Biotechnolgy of Fungal beta-Lactam Antibiotics and Related Peptide Synthetases. Advances in Biochemical Engineering, vol 88. Springer, Berlin, Heidelberg. https://doi.org/10.1007/b99259

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• DOI: https://doi.org/10.1007/b99259

• Published: 04 October 2004

• Publisher Name: Springer, Berlin, Heidelberg

• Print ISBN: 978-3-540-22032-9

• Online ISBN: 978-3-540-44406-0

• eBook Packages: Springer Book Archive

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