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Chemical induction of silent biosynthetic pathway transcription in Aspergillus niger

  • Original Paper
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Manipulation of the fungal epigenome is hypothesized to be an effective method for accessing natural products from silent biosynthetic pathways. A library of epigenetic modifiers was tested using the fungus Aspergillus niger to determine the impact of small-molecule inhibitors on reversing the transcriptional suppression of biosynthetic genes involved in polyketide (PKS), non-ribosomal peptide (NRPS), and hybrid PKS-NRPS (HPN) production. Examination of expressed sequence tag libraries from A. niger demonstrated that >70% of its PKS-, NRPS-, and HPN-encoding gene clusters were transcriptionally suppressed under standard laboratory culture conditions. Using a chemical epigenetic methodology, we showed that treatment of A. niger with suberoylanilide hydroxamic acid and 5-azacytidine led to the transcriptional upregulation of many secondary-metabolite-encoding biosynthetic gene clusters. Chemical epigenetic modifiers exhibited positional biases for upregulating chromosomally distal gene clusters. In addition, a phylogenetic-based preference was noted in the upregulation of reducing clade I PKS gene clusters, while reducing clade IV PKS gene clusters were largely unaffected. Manipulating epigenetic features in fungi is a powerful method for accessing the products of silent biosynthetic pathways. Moreover, this approach can be readily incorporated into modern microbial screening operations.

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Acknowledgments

This work was supported by the University of Oklahoma, College of Arts and Sciences and the University of Oklahoma Department of Chemistry and Biochemistry. We thank D. Dyer, J. Piel, and B. A. Roe for helpful comments throughout the preparation of this manuscript. We are also grateful for editorial and technical input from F. Schmitz during the writing of this paper.

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Authors and Affiliations

  1. School of Chemistry, University of Bristol, Cantocks Close, Bristol, BS8 1TS, UK

    K. M. Fisch

  2. Laboratory for Genomics and Bioinformatics, Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA

    A. F. Gillaspy, M. Gipson & L. Jackson

  3. Natural Products Discovery Group, Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, 73019, USA

    J. C. Henrikson, A. R. Hoover & R. H. Cichewicz

  4. Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, 73019, USA

    F. Z. Najar

  5. Zoologisches Forschungsmuseum Alexander Koenig, 53112, Bonn, Germany

    H. Wägele

  6. Graduate Program in Ecology and Evolutionary Biology, University of Oklahoma, Norman, OK, 73019, USA

    R. H. Cichewicz

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  1. K. M. Fisch
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Fisch, K.M., Gillaspy, A.F., Gipson, M. et al. Chemical induction of silent biosynthetic pathway transcription in Aspergillus niger . J Ind Microbiol Biotechnol 36, 1199–1213 (2009). https://doi.org/10.1007/s10295-009-0601-4

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