Abstract
Loss-of-function Aspergillus nidulans CclA, a Bre2 ortholog involved in histone H3 lysine 4 methylation, activated the expression of cryptic secondary metabolite clusters in A. nidulans. One new cluster generated monodictyphenone, emodin and emodin derivatives, whereas a second encoded two anti-osteoporosis polyketides, F9775A and F9775B. Modification of the chromatin landscape in fungal secondary metabolite clusters allows for a simple technological means to express silent fungal secondary metabolite gene clusters.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Change history
18 August 2009
In the version of this article initially published, the fourth author's last name is misspelled. The author's name should read "Yazmid Reyes-Dominguez." The error has been corrected in the HTML and PDF versions of the article.
References
Nierman, W.C et al. Nature 438, 1151–1156 (2005).
Rohlfs, M., Albert, M., Keller, N.P. & Kempken, F. Biol. Lett. 3, 523–525 (2007).
Keller, N.P., Turner, G. & Bennett, J.W Nat. Rev. Microbiol. 3, 937–947 (2005).
Bergmann, S. et al. Nat. Chem. Biol. 3, 213–217 (2007).
Bok, J.W. & Keller, N.P. Eukaryot. Cell 3, 527–535 (2004).
Bayram, O. et al. Science 320, 1504–1506 (2008).
Perrin, R.M. et al. PLoS Pathog. 3, e50 (2007).
Bok, J.W. et al. Chem. Biol. 13, 31–37 (2006).
Shwab, E.K. et al. Eukaryot. Cell 6, 1656–1664 (2007).
Roze, L.V., Arthur, A.E., Hong, S.Y., Chanda, A. & Linz, J.E. Mol. Microbiol. 66, 713–726 (2007).
Mueller, J.E., Canze, M. & Bryk, M. Genetics 173, 557–567 (2006).
Sims, R.J. III & Rienberg, D. Genes Dev. 20, 2779–2786 (2006).
Wood, A., Schneider, J. & Shilatifard, A. Biochem. Cell Biol. 83, 460–467 (2005).
Ottaviani, A., Gilson, E. & Magdinier, F. Biochimie 90, 93–107 (2008).
Schneider, J. et al. Mol. Cell 19, 849–856 (2005).
Brown, D.W., Adams, T.H. & Keller, N.P. Proc. Natl. Acad. Sci. USA 93, 14873–14877 (1996).
Krick, A. et al. J. Nat. Prod. 70, 353–360 (2007).
Lu, P. et al. Mol. Genet. Genomics 273, 207–216 (2005).
Couch, R.D. & Gaucher, G.M. J. Biotechnol. 108, 171–178 (2004).
Wu, Y. et al. Life Sci. 81, 1332–1338 (2007).
Fernandes, M., Keller, N.P. & Adams, T.H. Mol. Microbiol. 28, 1355–1365 (1998).
Sato, S., Morishita, T., Hosoya, T. & Ishikawa, Y. Novel pentacyclic compounds, F-9775A and F-9775B, their manufacture with Paecilomyces carneus, and their use for treatment of osteoporosis. Japanese patent JP11001480 (1999).
Dean, R.A. et al. Nature 434, 980–986 (2005).
Cuomo, C.A. et al. Science 317, 1400–1402 (2007).
Pelaez, F. Biological activities of fungal metabolites. In Handbook of Industrial Mycology (ed., Z. An) 49–92 (Marcel Dekker, New York, 2005).
Acknowledgements
This research was funded in part by the US National Science Foundation grant MCB-0236393 to N.P.K., National Institutes of Health grant GM084077 to N.P.K., B.R.O. and C.C.C.W., and GM031837 to B.R.O. Work in Vienna was supported by grant P19731-B11 from the Austrian Science Fund (FWF) to J.S.
Author information
Authors and Affiliations
Contributions
J.W.B. contributed to design and execution of experiments and to writing the manuscript. Y.-M.C., J.F.S. and H.-C.L. were involved in metabolite analysis of Aspergillus strains by LC-MS and in the isolation and structural determination of monodictyphenone, emodins and F9755A/B by one- and two-dimensional NMR. Y.R.-D. conducted the ChIP analysis. K.W. was involved in obtaining LC/MS data. E.S. and A.D.D. were involved in generating Aspergillus mutant strains. B.R.O., N.P.K., J.S. and C.C.C.W. contributed to design and writing.
Corresponding authors
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–4, Supplementary Tables 1–5 and Supplementary Methods (PDF 544 kb)
Rights and permissions
About this article
Cite this article
Bok, J., Chiang, YM., Szewczyk, E. et al. Chromatin-level regulation of biosynthetic gene clusters. Nat Chem Biol 5, 462–464 (2009). https://doi.org/10.1038/nchembio.177
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nchembio.177
This article is cited by
-
Exploring Potential of Aspergillus sclerotiorum: Secondary Metabolites and Biotechnological Relevance
Mycological Progress (2023)
-
Molecular regulation of fungal secondary metabolism
World Journal of Microbiology and Biotechnology (2023)
-
Insights to Gossypium defense response against Verticillium dahliae: the Cotton Cancer
Functional & Integrative Genomics (2023)
-
Recent advances on Pestalotiopsis genus: chemistry, biological activities, structure–activity relationship, and biosynthesis
Archives of Pharmacal Research (2023)
-
Copper starvation induces antimicrobial isocyanide integrated into two distinct biosynthetic pathways in fungi
Nature Communications (2022)