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Enhancing Nonribosomal Peptide Biosynthesis in Filamentous Fungi

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Nonribosomal Peptide and Polyketide Biosynthesis

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1401))

Abstract

Filamentous fungi are historically known as rich sources for production of biologically active natural products, so-called secondary metabolites. One particularly pharmaceutically relevant chemical group of secondary metabolites is the nonribosomal peptides synthesized by nonribosomal peptide synthetases (NRPSs). As most of the fungal NRPS gene clusters leading to production of the desired molecules are not expressed under laboratory conditions, efforts to overcome this impediment are crucial to unlock the full chemical potential of each fungal species. One way to activate these silent clusters is by overexpressing and deleting global regulators of secondary metabolism. The conserved fungal-specific regulator of secondary metabolism, LaeA, was shown to be a valuable target for sleuthing of novel gene clusters and metabolites. Additionally, modulation of chromatin structures by either chemical or genetic manipulation has been shown to activate cryptic metabolites. Furthermore, NRPS-derived molecules seem to be affected by cross talk between the specific gene clusters and some of these metabolites have a tissue- or developmental-specific regulation. This chapter summarizes how this knowledge of different tiers of regulation can be combined to increase production of NRPS-derived metabolites in fungal species.

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Acknowledgments

This research was funded by NIH PO1 GM084077 to NPK, by R01 Al065728-01 to NPK, and by NIH NRSA AI55397 to AAS.

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Authors and Affiliations

  1. Department of Genetics, University of Wisconsin-Madison, 1550 Linden Drive, Madison, WI, 53706, USA

    Alexandra A. Soukup

  2. Department of Bacteriology, University of Wisconsin-Madison, 1550 Linden Drive, Madison, WI, 53706, USA

    Nancy P. Keller

  3. Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, 3455 Microbial Sciences, 1550 Linden Drive, Madison, WI, 53706, USA

    Nancy P. Keller & Philipp Wiemann

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  1. Alexandra A. Soukup
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  2. Nancy P. Keller
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  3. Philipp Wiemann
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Correspondence to Nancy P. Keller .

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  1. Donald Danforth Plant Science Center, Saint Louis, Missouri, USA

    Bradley S. Evans

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Soukup, A.A., Keller, N.P., Wiemann, P. (2016). Enhancing Nonribosomal Peptide Biosynthesis in Filamentous Fungi. In: Evans, B. (eds) Nonribosomal Peptide and Polyketide Biosynthesis. Methods in Molecular Biology, vol 1401. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3375-4_10

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  • DOI: https://doi.org/10.1007/978-1-4939-3375-4_10

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