Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2009 Nov;4(11):1505-10.

Unlocking fungal cryptic natural products

Yi-Ming Chiang  1 , Kuan-Han Lee, James F Sanchez, Nancy P Keller, Clay C C Wang
Affiliations
Review

Unlocking fungal cryptic natural products

Yi-Ming Chiang et al. Nat Prod Commun. 2009 Nov.

Abstract

Recent published sequencing of fungal genomes has revealed that these microorganisms have a surprisingly large number of secondary metabolite pathways that can serve as potential sources for new and useful natural products. Most of the secondary metabolites and their biosynthesis pathways are currently unknown, possibly because they are produced in very small amounts and are thus difficult to detect or are produced only under specific conditions. Elucidating these fungal metabolites will require new molecular genetic tools, better understanding of the regulation of secondary metabolism, and state of the art analytical methods. This review describes recent strategies to mine the cryptic natural products and their biosynthetic pathways in fungi.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Chemical structures of medicinally important natural products: penicillin G (1), cyclosporine A (2), and lovastatin (3).
Figure 2
Figure 2
Compounds isolated from A. nidulans by combining bioinformatic analysis and the OSMAC approach.
Figure 3
Figure 3
Unlocking a fungal cryptic PKS-NRPS via activation of a pathway-specific regulator to produce aspyridones A (8) and B (9).
Figure 4
Figure 4
Unlocking fungal cryptic dual PKSs via activation of a pathway-specific regulator to produce asperfuranone (10).
Figure 5
Figure 5
>Increasing secondary metabolite production via overexpression of the global regulator, LaeA.
Figure 6
Figure 6
Unlocking fungal cryptic secondary metabolites via addition of DNA methyltransferase and histone deacetylase (HDAC) inhibitors to the culture medium.
Figure 7
Figure 7
Unlocking fungal cryptic secondary metabolites via epigenetic regulation: Deletion of CclA, a member of the COMPASS complex.
Figure 8
Figure 8
(A) Unlocking fungal cryptic secondary metabolites via deletion of SumO protein. (B) Proposed biosynthetic pathway of asperthecin (38) generated from genetic and chemical analysis.
See this image and copyright information in PMC

References

    1. Keller NP, Turner G, Bennett JW. Fungal secondary metabolism - from biochemistry to genomics. Nature Review Microbiology. 2005;3:937–947. - PubMed
    1. Schneider P, Misiek M, Hoffmeister D. In vivo and in vitro production options for fungal secondary metabolites. Molecular Pharmaceutics. 2008;5:234–242. - PubMed
    1. Galagan JE, Calvo SE, Cuomo C, Ma LJ, Wortman JR, Batzoglou S, Lee SI, Basturkmen M, Spevak CC, Clutterbuck J, Kapitonov V, Jurka J, Scazzocchio C, Farman M, Butler J, Purcell S, Harris S, Braus GH, Draht O, Busch S, D’Enfert C, Bouchier C, Goldman GH, Bell-Pedersen D, Griffiths-Jones S, Doonan JH, Yu J, Vienken K, Pain A, Freitag M, Selker EU, Archer DB, Penalva MA, Oakley BR, Momany M, Tanaka T, Kumagai T, Asai K, Machida M, Nierman WC, Denning DW, Caddick M, Hynes M, Paoletti M, Fischer R, Miller B, Dyer P, Sachs MS, Osmani SA, Birren BW. Sequencing of Aspergillus nidulans and comparative analysis with. A. fumigatus and A. oryzae. Nature. 2005;438:1105–1115. - PubMed
    1. Sanchez JF, Chiang YM, Wang CCC. Diversity of polyketide synthases found in the Aspergillus and Streptomyces genomes. Molecular Pharmaceutics. 2008;5:226–233. - PubMed
    1. Cox RJ. Polyketides, proteins and genes in fungi: programmed nano-machines begin to reveal their secrets. Organic & Biomolecular Chemistry. 2007;5:2010–2026. - PubMed

Publication types

Substances

LinkOut - more resources