Together with bacteria and plants, fungi are among the most prolific producers of secondary metabolites. Fungal metabolites both benefit (antibiotics, pharmaceuticals) and harm (toxins, carcinogens) mankind.
Although genes involved in primary metabolism are typically scattered throughout the fungal genome, genes involved in secondary metabolism are arranged in clusters. This format is reminiscent of the arrangement of bacterial secondary-metabolite operons.
Fungal secondary metabolites are derived from four main chemical classes: polyketides, non-ribosomal peptides, terpenes and indole alkaloids. Hallmark biosynthetic enzymes are associated with concomitant clusters, including polyketide synthases, non-ribosomal peptide synthetases, terpene cyclases and prenylation synthetases, respectively.
Biosynthetic genes within secondary-metabolite clusters are typically regulated by pathway-specific transcription factors of which the encoding gene might or might not be found within the cluster. Broad-domain transcription factors that are responsive to carbon, nitrogen and pH also act to regulate gene expression in these clusters.
Secondary metabolism is often accompanied by spore formation in fungi. Both processes are regulated by G-protein signal-transduction pathways in several fungi.
Recent genome sequencing has revealed that some species of Aspergillus contain more than 30 secondary metabolite gene clusters. LaeA, a novel methyltransferase that was recently characterized in the aspergilli, regulates many of these clusters simultaneously, perhaps through chromatin reorganization.
Bioinformatic analyses of the Aspergillus fumigatus, Aspergillus nidulans and Aspergillus oryzae genomes has revealed multiple putative polyketide synthases and non-ribosomal peptide synthetases. This finding will direct future studies in functional analysis.
Much of natural product chemistry concerns a group of compounds known as secondary metabolites. These low-molecular-weight metabolites often have potent physiological activities. Digitalis, morphine and quinine are plant secondary metabolites, whereas penicillin, cephalosporin, ergotrate and the statins are equally well known fungal secondary metabolites. Although chemically diverse, all secondary metabolites are produced by a few common biosynthetic pathways, often in conjunction with morphological development. Recent advances in molecular biology, bioinformatics and comparative genomics have revealed that the genes encoding specific fungal secondary metabolites are clustered and often located near telomeres. In this review, we address some important questions, including which evolutionary pressures led to gene clustering, why closely related species produce different profiles of secondary metabolites, and whether fungal genomics will accelerate the discovery of new pharmacologically active natural products.
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Turner, W. B. Fungal Metabolites (Academic Press, London, 1971).
Turner, W. B. & Aldridge, D. C. Fungal Metabolites II (Academic Press, London, 1983).
Cole, R. & Schweikert, M. Handbook of Secondary Fungal Metabolites Volumes 1–3 (Elsevier, Amsterdam, 2003).
Davies, J. Recombinant DNA and the Production of Small Molecules (ASM Press, Washington DC, 1985).
Bennett, J. W. & Bentley, R. What's in a name? Microbial secondary metabolism. Adv. Appl. Microbiol. 34, 1–28 (1989).
Ciba Foundation Symposium 171. Secondary Metabolites: Their Function and Evolution (John Wiley & Sons, Chicester, 1992).
Raistrick, H. A region of biosynthesis. Proc. R. Soc. Lond. B Biol. Sci. 136, 481–508 (1950).
Pelaez, F. Biological activities of fungal metabolites. in Handbook of Industrial Mycology (ed. An, Z.) 49–92 (Marcel Dekker, New York, 2005).
Fujii, I., Watanabe, A., Sankawa, U. & Ebizuka, Y. Identification of Claisen cyclase domain in fungal polyketide synthase WA, a naphthopyrone synthase of Aspergillus nidulans. Chem. Biol. 8, 189–197 (2001).
Kennedy, J. et al. Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis. Science 284, 1368–1372 (1999). The first biochemical dissection of fungal polyketide synthase and use of the model system A. nidulans to help decipher lovastatin assembly in A. terreus.
Bentley, R. & Bennett, J. W. Constructing polyketides: from Collie to combinatorial biosynthesis. Annu. Rev. Microbiol. 53, 411–446 (1999).
Donadio S., Staver, M. J., McAlpine, J. B., Swanson, S. J. & Katz, L. Modular organization of gene required for complex polyketide biosynthesis. Science 252, 675–679 (1991).
Brown, D. et al. Twenty-five co-regulated transcripts define a sterigmatocystin gene cluster in Aspergillus nidulans. Proc. Natl Acad. Sci. USA 93, 1418–1422 (1996).
Yu, J. et al. Clustered pathway genes in aflatoxin biosynthesis. Appl. Environ. Microbiol. 70, 1253–1262 (2004).
Yu, J., D. Bhatnagar, D. & Cleveland, T. D. Completed sequence of aflatoxin pathway gene cluster in Aspergillus parasiticus. FEBS Lett. 564, 126–130 (2004).
Finking, R. & Marahiel, M. Biosynthesis of nonribosomal peptides. Annu. Rev. Microbiol. 58, 453–488 (2004).
Smith, D. J., Earl, A. J., Turner, G. The multifunctional peptide synthetase performing the first step of penicillin biosynthesis in Penicillium chrysogenum is a 421073 dalton protein similar to Bacillus brevis peptide antibiotic synthetases. EMBO J. 9, 2743–2750 (1990). First indication of the multimodular structure of peptide synthetases: three modules were detected in this tripeptide synthetase.
Kallow, W., Kennedy, J., Arezi, B., Turner, G. & von Doehren, H. Thioesterase domain of δ-(L-a-aminoadipyl)-L-cysteinyl-D-valine synthetase: alteration of stereospecificity by site-directed mutagenesis. J. Mol. Biol. 297, 395–408 (2000).
Wiest, A. et al. Identification of peptaibols from Trichoderma virens and cloning of a peptaibol synthetase. J. Biol. Chem. 277, 20862–20868 (2002).
Weber, G., Schorgendorfer, K., Schneider-Scherzer, E. & Leitner, E. The peptide synthetase catalyzing cyclosporine production in Tolypocladium niveum is encoded by a giant 45.8-kilobase open reading frame. Curr. Genet. 26, 120–125 (1994).
Eisendle, M., Oberegger, H., Zadra, I. & Haas, H. The siderophore system is essential for viability of Aspergillus nidulans: functional analysis of two genes encoding L-ornithine N5-monooxygenase (sidA) and a nonribosomal peptide synthetase (sidC). Mol. Microbiol. 49, 359–375 (2003).
Tudzynski, B., Hedden, P. Carrera, E. & Gaskin, P. The 450–4 gene of Gibberella fujikuroi encodes ent-kaurine oxidase in the gibberellin biosynthesis pathway. Appl. Environ. Microbiol. 67, 3514–3522 (2001).
Rynkiewicz, M. J., Cane, D. E. & Christianson, D. W. Structure of trichodiene synthase from Fusarium sporotrichioides provides mechanistic inferences on the terpene cyclization cascade. Proc. Natl Acad. Sci. USA 98, 13543–13548 (2001).
Carruthers, J., Kang, I., Rynkiewicz, M., Cane, D. & Christianson, D. Crystal structure determination of aristolochene synthase from the cheese mold, Penicillium roquefortii. J. Biol. Chem. 275, 25533–25539 (2000). Structural determination of a fungal terpenecyclase, showing that whereas the primary sequences of terpene cyclases are not well conserved between plants and fungi, the tertiary structure is conserved. Also, terpene cyclases might all be derived from a common ancestor.
Schmidhauser, T., Lauter, F., Russo, V. & Yanofsky, C. Cloning, sequence, and photoregulation of al-1, a carotenoid biosynthetic gene of Neurospora crassa. Mol. Cell. Biol. 10, 5064–5070 (1990).
Young, C., McMillan, L., Telfer, E. & Scott, B. Molecular cloning and genetic analysis of an indole-diterpene gene cluster from Penicillium paxilli. Mol. Microbiol. 39, 754–764 (2001)
Tudzynski, P. et al. Evidence for an ergot alkaloid gene cluster in Claviceps purpurea. Mol. Gen. Genet. 261, 133–141 (1999). Identification of the ergot alkaloid gene cluster, which includes an NRPS required for ergotamine biosynthesis.
von Nussbaum, F. Stephacidin B — a new stage of complexity within prenylated indole alkaloids from fungi. Angew. Chem. Int. Ed. Engl. 42, 3068–3071 (2003).
Bennett, J. W., Chang, P. -K. & Bhatnagar, D. One gene to whole pathway: the role of norsolorinic acid in aflatoxin research. Adv. Appl. Microbiol. 45, 1–15 (1997).
Luengo, J. M. & Penalva, M. A. Penicillin Biosynthesis in Aspergillus: 50 Years On (eds Martinelli, S. D & Kinghorn, J. R.) 603–638 (Elsevier, Amsterdam,1994).
Rehacek, Z. & Sajdl, P. Ergot Alkaloids: Chemistry, Biological Effects, Biotechnology (Academia, Prague, 1990)
Keller, N. & Hohn, T. Metabolic pathway gene clusters in filamentous fungi. Fungal Genet. Biol. 21, 17–29 (1997).
Zhang, Y. -Q., Wilkinson, H., Keller, N. P. & Tsitsigiannis, D. Secondary metabolite gene clusters. in Handbook of Industrial Microbiology (ed. An, Z.) 355–386 (Marcel Dekker, New York, 2005).
Gutierrez, S., Velasco, J., Fernandez, F. J. & Martin, J. F. The cefG gene of Cephalosporium acremonium is linked to the cefEF gene and encodes a deacetylcephalosporin C acetyltransferase closely related to homoserine O-acetyltransferase. J. Bacteriol. 174, 3056–3064 (1992).
Abe, Y. et al. Effect of increased dosage of the ML-236B (compactin) biosynthetic gene cluster on ML-236B production in Penicillium citrinum. Mol. Gen. Genet. 268, 130–137 (2002).
Abe, Y., Ono, C., Hosobuchi, M. & Yoshikawa, H. Functional analysis of mlcR, a regulatory gene for ML-236B (compactin) biosynthesis in Penicillium citrinum. Mol. Genet. Genomics 268, 352–361 (2002).
Proctor, R. H., Brown, D. W., Plattner, R. D. & Desjardins, A. E. Co-expression of 15 contiguous genes delineates a fumonisin biosynthetic gene cluster in Gibberella moniliformis. Fungal Genet. Biol. 38, 237–249 (2003).
Hedden, P., Phillips, A., Rojas, M., Carrera, C. & Tudzynski, B. Gibberellin biosynthesis in plants and fungi: a case of convergent evolution? J. Plant Growth Regul. 20, 319–331 (2002).
Tudzynski, B. Biosynthesis of gibberellins in Gibberella fujikuroi: biomolecular aspects. Appl. Environ. Microbiol. 52, 298–310 (1999).
Ahn, J., Cheng, Y. & Walton, J. An extended physical map of the TOX2 locus of Cochliobolus carbonum required for biosynthesis of HC-toxin. Fungal Genet. Biol. 35, 31–38 (2002).
Kimura, N. & Tsuge, T. Gene cluster involved in melanin biosynthesis of the filamentous fungus Alternaria alternata. J. Bacteriol. 175, 4427–4435 (1993).
Tsai, H., Wheeler, M., Chang, Y. & Kwon-Chung, K. A developmentally regulated gene cluster involved in conidial pigment biosynthesis in Aspergillus fumigatus. J. Bacteriol. 181, 6469–6477 (1999).
Smith, D. J. et al. β-lactam antibiotic biosynthetic genes have been conserved in clusters in prokaryotes and eukaryotes. EMBO J. 9, 741–747 (1990). Showed that secondary metabolic genes were clustered in filamentous fungi, and revealed the close relationship between the β-lactam biosynthetic genes of bacteria and fungi.
Brakhaage, A. A. Molecular regulation of β-lactam biosynthesis in filamentous fungi. Microbiol. Mol. Biol. Rev. 62, 547–585 (1998).
Gardiner, D., Cozijnsen, A., Wilson, L., Pedras, M. & Howlett, B. The sirodesmin biosynthetic gene cluster of the plant pathogenic fungus Leptosphaeria maculans. Mol. Microbiol. 53, 1307–1318 (2004).
Trapp, S., Hohn T., McCormick, S. & Jarvis, B. Characterization of the gene cluster for biosynthesis of macrocyclic trichothecenes in Myrothecium roridum. Mol. Gen. Genet. 257, 421–432 (1998).
Brown, D., McCormick, S., Alexander, N., Proctor, R. & Desjardins, A. A genetic and biochemical approach to study trichothecene diversity in Fusarium sporotrichioides and Fusarium graminearum. Fungal Genet. Biol. 32, 121–133 (2001).
Proctor, R, Hohn, T., McCormick, S. & Desjardins, A. Tri6 encodes an unusual zinc finger protein involved in regulation of trichothecene biosynthesis in Fusarium sporotrichioides. Appl. Environ. Microbiol. 61, 1923–1930 (1995).
Woloshuk, C. et al. Molecular characterization of aflR, a regulatory locus for aflatoxin biosynthesis. Appl. Environ. Microbiol. 60, 2408–2414 (1994). Identification of the first Zn(II) 2 Cys 6 that regulates a secondary metabolite gene cluster.
Fernandes, M., Keller, N. & Adams, T. Sequence-specific binding by Aspergillus nidulans AflR, a C6 zinc cluster protein regulating mycotoxin biosynthesis. Mol. Microbiol. 28, 1355–1365 (1998).
Chang, P., Ehrlich, K., Yu, J., Bhatnagar, D. & Cleveland, T. Increased expression of Aspergillus parasiticus aflR, encoding a sequence-specific DNA-binding protein, relieves nitrate inhibition of aflatoxin biosynthesis. Appl. Environ. Microbiol. 61, 2372–2377 (1995).
Yu, J. et al. Conservation of structure and function of the aflatoxin regulatory gene aflR from Aspergillus nidulans and A. flavus. Curr. Genet. 29, 549–555 (1996).
Pedley, K. & Walton, J. Regulation of cyclic peptide biosynthesis in a plant pathogenic fungus by a novel transcription factor. Proc. Natl Acad. Sci. USA 98, 14174–14179 (2001).
Schmitt, E. K., Hoff, B. & Kuck, U. AcFKH1, a novel member of the forkhead family, associates with the RFX transcription factor CPCR1 in the cephalosporin C-producing fungus Acremonium chrysogenum. Gene 342, 269–281 (2004). In contrast to penicillin regulation in A. nidulans , cephalosporin regulation is by a forkhead transcription factor in Acremonium.
Litzka, O., Papagiannopolus, P., Davis, M., Hynes, M. & Brakhage, A. The penicillin regulator PENR1 of Aspergillus nidulans is a HAP-like transcriptional complex. Eur. J. Biochem. 251, 758–767 (1998). A HAP-like CCAAT-binding complex regulates penicillin biosynthesis.
Brakhage, A. et al. HAP-like CCAAT-binding complexes in filamentous fungi: implications for biotechnology. Fungal Genet. Biol. 27, 243–252 (1999).
Bennett, J. & Ciegler, A. (eds) Secondary Metabolism and Differentiation in Fungi. (Marcel Dekker, New York, 1983).
Berry, D. R. (ed.) Physiology of Industrial Fungi (Blackwell Scientific Publishing, Oxford, 1988).
Ehrlich, K., Montalbano, B. & Cotty, P. Sequence comparison of aflR from different Aspergillus species provides evidence for variability in regulation of aflatoxin production. Fungal Genet. Biol. 38, 63–74 (2003).
Tudzynski, B., Homann, V., Feng, B. & Marzluf, G. Isolation, characterization and disruption of the areA nitrogen regulatory gene of Gibberella fujikuroi. Mol. Gen. Genet. 261, 106–114 (1999).
Dowzer, C. & Kelly, J. Cloning of the creA gene from Aspergillus nidulans: a gene involved in carbon catabolite repression. Curr. Genet. 15, 457–459 (1989).
Kudla, B. et al. The regulatory gene areA mediation nitrogen metabolite repression in Aspergillus nidulans. Mutations affecting specificity of gene activation alter a loop residue of a putative zinc finger. EMBO J. 9, 1355–1364 (1990).
Tilburn, J. et al. The Aspergillus PacC zinc finger transcription factor mediates regulation of both acid- and alkaline-expressed genes by ambient pH. EMBO J. 14, 779–790 (1995). Important contribution that showed that pH regulates the penicillin gene cluster through a global transcription factor, PacC.
Martin, J. Molecular control of expression of penicillin biosynthesis genes in fungi: regulatory proteins interact with a bidirectional promoter region. J. Bacteriol. 182, 2355–2362 (2000).
Luckner, M. Secondary Metabolism in Microorganisms, Plants and Animals (Springer–Verlag, Berlin, 1990).
Kale, S., Bhatnagar D. & Bennett, J. Isolation and characterization of morphological variants of Aspergillus parasiticus deficient in secondary metabolite production. Mycol. Res. 98, 645–652 (1994).
Kale, S., Cary, J., Bhatnagar, D. & Bennett, J. Characterization of an experimentally induced, nonaflatoxigenic variant strains of Aspergillus parasiticus. Appl. Environ. Microbiol. 62, 3999–3404 (1996).
Kale, S. et al. Genetic analysis of morphological variants of Aspergillus parasiticus deficient in secondary metabolite production. Mycol. Res. 107, 831–840 (2003).
Zhou, R., Rasooly, R. & Linz, J. Isolation and analysis of fluP, a gene associated with hyphal grown and sporulation in Aspergillus parasiticus. Mol. Gen. Genet. 264, 514–520 (2000).
Calvo, A., Wilson, R., Bok, J. & Keller, N. Relationship between secondary metabolism and fungal development. Mol. Microbiol. Rev. 66, 447–459 (2002).
Hicks, J., Yu, J., Keller, N. & Adams, T. Aspergillus sporulation and mycotoxin production both require inactivation of the FadA G α protein-dependent signaling pathway. EMBO J. 16, 4916–4923 (1997). This paper reported the genetic connection of sporulation and secondary metabolism through a G-protein signalling pathway.
Shimizu, K. & Keller, N. Genetic involvement of a cAMP-dependent protein kinase in a G protein signaling pathway regulating morphological and chemical transitions in Aspergillus nidulans. Genetics 157, 591–600 (2001).
Roze, L., Beaudry, R., Keller, N. & Linz, J. Regulation of aflatoxin synthesis by FadA/cAMP/protein kinase A signaling in Aspergillus parasiticus. Mycopathologia 158, 219–232 (2004).
Shimizu, K., Hicks, J., Huang T. -P. & Keller, N. P. Pka, Ras and RGS protein interactions regulate activity of AflR, a Zn(II)2Cys6 transcription factor in Aspergillus nidulans. Genetics 165, 1095–1104 (2003).
Bok, J. & Keller, N. LaeA, a regulator of secondary metabolism in Aspergillus. Euk. Cell 3, 527–535 (2004). Discovery of novel global regulator of several Aspergillus secondary metabolites.
Tag, A. et al. G-protein signalling mediates differential production of toxic secondary metabolites. Mol. Microbiol. 38, 658–665 (2000).
Schulze Gronover, C., Schorn, C. & Tydzynski, B. Identification of Botrytis cinerea genes up-regulated during infection and controlled by the G α subunit BCG1 using suppression subtractive hybridization (SSH). Mol. Plant Microbe Interact. 17, 537–546 (2004).
Reithner, B. et al. The G protein α subunit Tga1 of Trichoderma atroviride is involved in chitinase formation and differential production of antifungal metabolites. Fungal Genet. Biol. 42, 749–760 (2005).
Gao, S. & Nuss, D. Distinct roles for two G protein α subunits in fungal virulence, morphology, and reproduction revealed by targeted gene disruption. Proc. Natl Acad. Sci. USA 93, 14122–14127 (1996).
Lawrence, J. G. & Roth, J. R. Selfish operons: horizontal transfer may drive the evolution of gene clusters. Genetics 143, 1843–1860 (1996).
Lawrence, J. G. Selfish operons and speciation by gene transfer. Trends Microbiol. 5, 355–359 (1997).
Lawrence, J. G. Gene transfer, speciation, and the evolution of bacterial genomes. Curr. Opin. Microbiol. 2, 519–523 (1999).
Rosewich, U. & Kistler, H. Role of horizontal gene transfer in the evolution of fungi. Annu. Rev. Phytopathol. 38, 325–363 (2000).
Walton, J. J. Horizontal gene transfer and the evolution of secondary metabolite gene clusters in fungi: an hypothesis. Fungal Genet. Biol. 30, 167–171 (2000).
Smith, M. W., Feng, D. -F. & Doolittle, R. F. Evolution by acquisition: the case for horizontal gene transfers. Trends Biochem. Sci. 17, 489–493 (1992).
Litt, M., Simpson, M., Gaszner, M., Allis, D. & Felsenfeld, G. Correlation between histone lysine methylation and developmental changes at the chicken β-globin locus. Science 293, 2453–2455 (2001).
Recillas-Targa, F. et al. Position-effect protection and enhancer blocking by the chicken β-globin insulator are separable activities. Proc. Natl Acad. Sci. USA 99, 6883–6888 (2002).
Noma, K., Allis, C. & Grewal, S. Transitions in distinct histone H3 methylation patterns at the heterochromatin domain boundaries. Science 293, 1150–1155 (2001).
Lee, D. Y., Teyssier, C., Strahl, B. D. & Stallcup, M. R. Role of protein methylation I regulation of transcription. Endocr. Rev. 26, 147–170 (2005).
Spilsbury, J. F. & Wilkinson, S. The isolation of festuclavine and two new clavine alkaloids from Aspergillus fumigatus Fres. J. Chem. Soc. 5, 2085–2091 (1961).
Cole, R. J. et al. Mycotoxins produced by Aspergillus fumigatus species isolated from molded silage. J. Agric. Food Chem. 25, 826–830 (1977).
Challis, G. L, Ravel, J. & Townsend, C. A. Predictive, structure-based model of amino acid recognition by nonribosomal peptide synthetase adenylation domains. Chem. Biol. 7, 211–224 (2000).
Song, Z., Cox, R. J., Lazarus, C. M. & Simpson, T. J. Fusarin C biosynthesis in Fusarium moniliforme and Fusarium venenatum. ChembioChem. 5, 1196–1203 (2004).
Bohnert, H. U. et al. A putative polyketide synthase/peptide synthetase from Magnaporthe grisea signals pathogen attack to resistant rice. Plant Cell 16, 2499–2513 (2004).
Hobby, G. Penicillin: Meeting the Challenge (Yale University Press, New Haven, 1985).
Wainwright, M. Miracle Cure: the Story of Penicillin and the Golden Age of Antibiotics (Blackwell Publishing, Oxford, 1990).
Bennett, J. & Chung, K. Alexander Fleming and the discovery of penicillin. Adv. Appl. Microbiol. 49, 163–184 (2001).
Lax, A. The Mold in Dr Florey's Coat. The Story of the Penicillin Miracle (Henry Holt & Company, New York, 2004)
Scoutaris, M. “Moldy Mary” and the Illinois Fruit and Vegetable Company. Pharm. Hist. 38, 175–177 (1996).
Bentley, R. The molecular structure of penicillin. J. Chem. Ed. 81, 1462–1470 (2004).
Kuiper-Goodman, T. Food safety: mycotoxins and phycotoxins in perspective. In Mycotoxins and Phycotoxins — Developments in Chemistry, Toxicology and Food Safety. (eds Miraglia, M., van Edmond, H., Brera, C. & Gilbert, J.) 25–48 (Alaken Inc., Fort Collins, 1998)
Squire, R. A. Ranking animal carcinogens. A proposed regulatory approach. Science 214, 877–880 (1981).
Eaton, D. & Groopman, J. (eds) The Toxicology of Aflatoxins: Human Health, Veterinary, and Agricultural Significance (Academic Press, San Diego, 1998).
Payne, G. & Brown, M. Genetics and physiology of aflatoxin biosynthesis. Annu. Rev. Plant Path. 36, 329–362 (1998).
Hicks, J., Shimizu, K. & Keller, N. Genetics and biosynthesis of aflatoxins and sterigmatocystin. in The Mycota. Volume XI. Agricultural Applications, (ed. Kempken, F.) 55–69 (Springer–Verlag, Berlin, 2002).
Zilinskas, R. A. Iraq's biological weapons. The past as future? J. Amer. Med. Assoc. 278, 418–424 (1997).
Green, G. The Human Factor (Everyman's Library, London, 1979).
Centers for Disease Control and Prevention (CDC). Outbreak of aflatoxin poisoning — eastern and central provinces, Kenya. January–July 2004. Morb. Mortal. Wkly Rep. 53, 790–793 (2004).
Bennett, J. W. & Bentley, R. Pride and prejudice: the story of ergot. Persp. Biol. Med. 42, 333–355 (1999).
Ulrich, R. F. & Paten, B. M. The rise, decline and fall of LSD. Persp. Biol. Med. 34, 561–578 (1991).
Caporeal, L. Ergotism: the Satan loosed in Salem? Science 192, 21–26 (1976).
Matossian, M. Ergot and the Salem witchcraft affair. Am. Scientist 70, 355–357 (1982).
Cook, R. Acceptable Risk (Barkley, New York, 1996).
Nierman, W. C. et al. Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature (in the press).
Galagan, J. et al. Sequencing and comparative analysis of Aspergillus nidulans. Nature (in the press).
Machida, M. et al. Genome sequencing and analysis of Aspergillus oryzae. Nature (in the press).
Genomic data for Aspergillus fumigatus were provided by The Institute for Genomic Research and The Wellcome Trust Sanger Institute; genomic data for Aspergillus nidulans were provided by The Broad Institute; and genomic data for Aspergillus oryzae were provided by The National Institute of Advanced Industrial Science and Technology. Coordination of the analyses of these data was enabled by an international collaboration involving more than 50 institutions from 10 countries and coordinated from Manchester, UK.
The authors declare no competing financial interests.
- ERGOT ALKALOID
Any of a group of about 30 indole alkaloids obtained from the sclerotial phase of the fungus Claviceps purpurea.
- INTERMEDIARY METABOLISM
Enzyme-catalysed processes within cells that metabolize macronutrients, carbohydrate, fat and protein.
Describes secondary metabolites released by plants, bacteria, fungi or viruses that have a direct or indirect, harmful or even beneficial effect on another organism.
In a polyketide synthase or non-ribosomal peptide synthetase, a stretch of conserved amino acids that defines a specific biochemical function or active site region.
In a polyketide synthase or non-ribosomal peptide synthetase, the complete set of domains that is required for one round of chain elongation and modification.
- CLAISEN-TYPE CYCLIZATION
Claisen condensations are a common mechanism in biological systems for synthesis of carbon–carbon bonds. The product is a β-ketoester. A similar reaction is also used to cyclize the heptaketide product of the wA gene to form an aromatic ring.
- PROTEINOGENIC AMINO ACIDS
Those amino acids that are found in proteins and that are coded for in the standard genetic code. Proteinogenic means 'protein-building'.
The enzymatic addition of prenyl moieties to secondary metabolic intermediates.
Describes chromosome regions with actively transcribed genes. Generally these regions stain poorly or not at all.
Describes chromosomal regions that are generally genetically inert. The chromatin is tightly coiled throughout the cell cycle and stains well.
Genes that are derived from a common ancestor by duplication. They can have related functions.
Genes that are derived from a common ancestor by a speciation event. They usually have equivalent function in their respective species.
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Keller, N., Turner, G. & Bennett, J. Fungal secondary metabolism — from biochemistry to genomics. Nat Rev Microbiol 3, 937–947 (2005). https://doi.org/10.1038/nrmicro1286
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