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Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans

Nature Chemical Biology volume 3, pages 213–217 (2007)Cite this article

Abstract

In the postgenomic era it has become increasingly apparent that the vast number of predicted biosynthesis genes of microorganisms is not reflected by the metabolic profile observed under standard fermentation conditions. In the absence of a particular (in most cases unknown) trigger these gene loci remain silent. Because these cryptic gene clusters may code for the biosynthesis of important virulence factors, toxins, or even drug candidates, new strategies for their activation are urgently needed to make use of this largely untapped reservoir of potentially bioactive compounds1,2. The discovery of new microbial metabolites through genome mining has proven to be a very promising approach3,4,5,6,7,8,9,10,11,12,13,14,15. Even so, the investigation of silent gene clusters is still a substantial challenge, particularly in fungi16. Here we report a new strategy for the successful induction of a silent metabolic pathway in the important model organism Aspergillus nidulans, which led to the discovery of novel PKS-NRPS hybrid metabolites.

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Figure 1: Organization of the apd gene locus in A. nidulans.
Figure 2: Monitoring the induction of aspyridone biosynthesis.
Figure 3

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Acknowledgements

We thank A. Perner for MS and HPLC/MS measurements, F.A. Gollmick for NMR measurements, and M.-G. Schwinger for strain cultivation. Financial support by the Leibniz Gemeinschaft, the Deutsche Forschungsgemeinschaft and the European Union (Euketides network) is gratefully acknowledged.

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Authors and Affiliations

  1. Leibniz Institute for Natural Product Research and Infection Biology (Hans-Knöll-Institute), Beutenbergstr. 11a, Jena, 07745, Germany

    Sebastian Bergmann, Julia Schümann, Kirstin Scherlach, Corinna Lange, Axel A Brakhage & Christian Hertweck

  2. Friedrich-Schiller-University, Jena, 07737, Germany

    Axel A Brakhage & Christian Hertweck

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  1. Sebastian Bergmann
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  4. Corinna Lange
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Contributions

S.B. and J.S. carried out the molecular studies; K.S. and C.L. performed structural elucidation; A.B. and C.H. designed the experiments and wrote the article.

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Correspondence to Christian Hertweck.

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Supplementary information

Supplementary Fig. 1

Gene expression profiling by northern blot analysis. (PDF 179 kb)

Supplementary Fig. 2

One-dimensional and two-dimensional NMR spectra of aspyridone A and HPLC profile. (PDF 138 kb)

Supplementary Table 1

Proposed functions of the apd gene products. (PDF 105 kb)

Supplementary Table 2

Bacterial and fungal strains and plasmids used in this study. (PDF 53 kb)

Supplementary Table 3

Oligonucleotides used in this study. (PDF 10 kb)

Supplementary Methods (PDF 16 kb)

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Bergmann, S., Schümann, J., Scherlach, K. et al. Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans. Nat Chem Biol 3, 213–217 (2007). https://doi.org/10.1038/nchembio869

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