Abstract
Fungi, eukaryotic organisms with a kingdom of their own, include microorganisms from moulds and yeasts to the most known and appreciated mushrooms. The incredible biodiversity of these organisms is not limited to their morphology but is reflected in their chemistry, namely in the variety of compounds they produce. Therefore, like other living beings, fungi can be an excellent source of bioactive compounds.
Although they may be primary metabolites, fungal bioactive compounds are mainly produced through secondary metabolism. These compounds have an essential role in the fungal survival and adaptation to almost all habitats on earth. Besides, they can also exert beneficial effects on human health, such as antioxidant, antimicrobial, anti-UV radiation, or even anti-inflammatory or antitumor activity. Given the wide bioactivity of the molecules produced, fungi have become, over time, an exciting source of compounds with possible application in various industries, including the food, pharmaceutical, or cosmetics industries.
Fungal secondary metabolites are mainly produced via acetyl-CoA and via the shikimate pathway. Even though it is possible to find in the literature some different classifications regarding secondary metabolites of fungi, in this manuscript, we define polyketides, non-ribosomal peptides, terpenoids, and indole alkaloids as the main structural classes.
The present chapter will present a brief introduction to fungal secondary metabolism, including some examples of the most well-known compounds and their principal functions in ecosystems. The biosynthetic pathways of the main classes of fungal secondary metabolites will also be depicted.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Al Khoury C, Bashir Z, Tokajian S, Nemer N, Merhi G, Nemer G (2022) In silico evidence of beauvericin antiviral activity against SARS-CoV-2. Comput Biol Med 141(August 2021):105171. https://doi.org/10.1016/j.compbiomed.2021.105171
Amengual. (2019) Bioactive properties of carotenoids in human health. Nutrients 11(10):2388. https://doi.org/10.3390/nu11102388
Avalos J, Limón MC (2021) Fungal secondary metabolism. Encyclopedia 2(1):1–13. https://doi.org/10.3390/encyclopedia2010001
Barajas JF, Shakya G, Moreno G, Rivera H, Jackson DR, Topper CL, Vagstad AL, la Clair JJ, Townsend CA, Burkart MD, Tsai S-C (2017) Polyketide mimetics yield structural and mechanistic insights into product template domain function in nonreducing polyketide synthases. Proc Natl Acad Sci 114(21). https://doi.org/10.1073/pnas.1609001114
Bérdy J (2012) Thoughts and facts about antibiotics: where we are now and where we are heading. J Antibiot 65(8):385–395. https://doi.org/10.1038/JA.2012.27
Bhattarai K, Bhattarai K, Kabir ME, Bastola R, Baral B (2021) Fungal natural products galaxy: biochemistry and molecular genetics toward blockbuster drugs discovery (pp. 193–284). https://doi.org/10.1016/bs.adgen.2020.11.006
Bills GF, Gloer JB (2016) Biologically active secondary metabolites from the fungi. Microbiol Spectrum 4(6). https://doi.org/10.1128/microbiolspec.FUNK-0009-2016
Bills GF, Gloer JB (2017) Biologically active secondary metabolites from the fungi. The Fungal Kingdom 1087–1119. https://doi.org/10.1128/9781555819583.CH54
Bills G, Li Y, Chen L, Yue Q, Niu XM, An Z (2014) New insights into the echinocandins and other fungal non-ribosomal peptides and peptaibiotics. Nat Prod Rep 31(10):1348–1375. https://doi.org/10.1039/c4np00046c
Boecker S, Grätz S, Kerwat D, Adam L, Schirmer D, Richter L, Schütze T, Petras D, Süssmuth RD, Meyer V (2018) Aspergillus niger is a superior expression host for the production of bioactive fungal cyclodepsipeptides. Fungal Biol Biotechnol 5(1):1–14. https://doi.org/10.1186/s40694-018-0048-3
Brakhage AA (2013) Regulation of fungal secondary metabolism. Nat Rev Microbiol 11(1):21–32. https://doi.org/10.1038/nrmicro2916
Bräse S, Encinas A, Keck J, Nising CF (2009) Chemistry and biology of mycotoxins and related fungal metabolites. Chem Rev 109(9):3903–3990. https://doi.org/10.1021/CR050001F
Bräse S, Gläser F, Kramer C, Lindner S, Linsenmeier AM, Masters K-S, Meister AC, Ruff BM, Zhong S (2013) The chemistry of mycotoxins 97. https://doi.org/10.1007/978-3-7091-1312-7
Brown R, Priest E, Naglik JR, Richardson JP (2021) Fungal toxins and host immune responses. Front Microbiol 12. https://doi.org/10.3389/fmicb.2021.643639
Büchter C, Koch K, Freyer M, Baier S, Saier C, Honnen S, Wätjen W (2020) The mycotoxin beauvericin impairs development, fertility and life span in the nematode Caenorhabditis elegans accompanied by increased germ cell apoptosis and lipofuscin accumulation. Toxicol Lett 334(September):102–109. https://doi.org/10.1016/j.toxlet.2020.09.016
Bushley KE, Ripoll DR, Turgeon BG (2008) Module evolution and substrate specificity of fungal nonribosomal peptide synthetases involved in siderophore biosynthesis. BMC Evol Biol 8(1):1–24. https://doi.org/10.1186/1471-2148-8-328
Cacciola F, Sandmann G (2022) Carotenoids and their biosynthesis in fungi. Molecules 27(4):1431. https://doi.org/10.3390/MOLECULES27041431
Cai R, Jiang H, Mo Y, Guo H, Li C, Long Y, Zang Z, She Z (2019) Ophiobolin-type Sesterterpenoids from the Mangrove endophytic fungus Aspergillus sp. ZJ-68. J Nat Prod 82(8):2268–2278. https://doi.org/10.1021/ACS.JNATPROD.9B00462/SUPPL_FILE/NP9B00462_SI_002.CIF
Casas López J, Sánchez Pérez J, Fernández Sevilla J, Acién Fernández F, Molina Grima E, Chisti Y (2004) Fermentation optimization for the production of lovastatin by Aspergillus terreus: use of response surface methodology. J Chem Technol Biotechnol 79(10):1119–1126. https://doi.org/10.1002/jctb.1100
Challis GL, Naismith JH (2004) Structural aspects of non-ribosomal peptide biosynthesis. Curr Opin Struct Biol 14(6):748–756. https://doi.org/10.1016/j.sbi.2004.10.005.Structural
Cheng JZ, Coyle CM, Panaccione DG, O’Connor SE (2010) Controlling a structural branch point in ergot alkaloid biosynthesis. J Am Chem Soc 132(37):12835–12837. https://doi.org/10.1021/JA105785P/SUPPL_FILE/JA105785P_SI_001.PDF
Cole RJ, Jarvis BB, Schweikert MA (2003) Handbook of Secondary Fungal Metabolites 1–3, 1–672
Cordero RJB, Casadevall A (2017) Functions of fungal melanin beyond virulence. Fungal Biol Rev 31(2):99–112. https://doi.org/10.1016/j.fbr.2016.12.003
Cox RJ (2007) Polyketides, proteins and genes in fungi: programmed nano-machines begin to reveal their secrets. Org Biomol Chem 5(13):2010. https://doi.org/10.1039/b704420h
Cox RJ, Skellam E, Williams K (2018) Biosynthesis of fungal polyketides. In: Physiology and genetics. Springer, pp 385–412. https://doi.org/10.1007/978-3-319-71740-1_13
Coyle CM, Panaccione DG (2005) An ergot alkaloid biosynthesis gene and clustered hypothetical genes from Aspergillus fumigatus. Appl Environ Microbiol 71(6):3112. https://doi.org/10.1128/AEM.71.6.3112-3118.2005
Coyle CM, Cheng JZ, O’Connor SE, Panaccione DG (2010) An old yellow enzyme gene controls the branch point between Aspergillus fumigatus and Claviceps purpurea ergot alkaloid pathways. Appl Environ Microbiol 76(12):3898–3903. https://doi.org/10.1128/AEM.02914-09
Crawford JM, Townsend CA (2010) New insights into the formation of fungal aromatic polyketides. Nat Rev Microbiol 8(12):879–889. https://doi.org/10.1038/nrmicro2465
Daley DK, Brown KJ, Badal S (2017) Fungal metabolites. In: Pharmacognosy. Elsevier, pp 413–421. https://doi.org/10.1016/B978-0-12-802104-0.00020-2
Devi R, Kaur T, Guleria G, Rana KL, Kour D, Yadav N, Yadav AN, Saxena AK (2020) Fungal secondary metabolites and their biotechnological applications for human health. New Future Dev Microb Biotechnol Bioeng 147–161. https://doi.org/10.1016/B978-0-12-820528-0.00010-7
von Döhren H (2004) Biochemistry and general genetics of nonribosomal peptide synthetases in fungi. Adv Biochem Eng Biotechnol 88:217–264. https://doi.org/10.1007/b99262
Dufossé L, Fouillaud M, Caro Y, Mapari SA, Sutthiwong N (2014) Filamentous fungi are large-scale producers of pigments and colorants for the food industry. Curr Opin Biotechnol 26:56–61. https://doi.org/10.1016/j.copbio.2013.09.007
Dunn MF, Niks D, Ngo H, Barends TRM, Schlichting I (2008) Tryptophan synthase: the workings of a channeling nanomachine. Trends Biochem Sci 33(6):254–264. https://doi.org/10.1016/J.TIBS.2008.04.008
Eisfeld K (2009) Non-ribosomal peptide synthetases of fungi. Physiol Genet 305–330. https://doi.org/10.1007/978-3-642-00286-1_15
Evidente A, Kornienko A, Lefranc F, Cimmino A, Dasari R, Evidente M, Mathieu V, Kiss R (2015) Sesterterpenoids with anticancer activity. Curr Med Chem 22(30):3502–3522. https://doi.org/10.2174/0929867322666150821101047
Fan Y, Liu X, Keyhani NO, Tang G, Pei Y, Zhang W, Tong S (2017) Regulatory cascade and biological activity of Beauveria bassiana oosporein that limits bacterial growth after host death. Proc Natl Acad Sci 114(9). https://doi.org/10.1073/pnas.1616543114
Farh ME-A, Jeon J (2020) Roles of fungal volatiles from perspective of distinct lifestyles in filamentous fungi. Plant Pathol J 36(3):193–203. https://doi.org/10.5423/PPJ.RW.02.2020.0025
Farzam K, Nessel TA, Quick J (2021) Erythromycin. Stat Pearls https://www.ncbi.nlm.nih.gov/books/NBK532249/
Feng Y, Huang Y, Zhan H, Bhatt P, Chen S (2020) An overview of Strobilurin fungicide degradation: current status and future perspective. Front Microbiol 11. https://doi.org/10.3389/fmicb.2020.00389
Flieger M, Wurst M, Shelby R (1997) Ergot alkaloids – sources, structures and analytical methods. Folia Microbiol 42(1):3–30. https://doi.org/10.1007/BF02898641
Fujii I (2010) Functional analysis of fungal polyketide biosynthesis genes. J Antibiot 63(5):207–218. https://doi.org/10.1038/ja.2010.17
Fujii I, Watanabe A, Sankawa U, Ebizuka Y (2001) Identification of Claisen cyclase domain in fungal polyketide synthase WA, a naphthopyrone synthase of Aspergillus nidulans. Chem Biol 8(2):189–197. https://doi.org/10.1016/S1074-5521(00)90068-1
Fujii I, Watanabe A, Ebizuka Y (2004) More functions for multifunctional polyketide synthases. In: Advances in fungal biotechnology for industry, agriculture, and medicine. Springer, pp 97–125. https://doi.org/10.1007/978-1-4419-8859-1_6
Gao L, Guo J, Fan Y, Ma Z, Lu Z, Zhang C, Zhao H, Bie X (2018) Module and individual domain deletions of NRPS to produce plipastatin derivatives in Bacillus subtilis. Microb Cell Factories 17(1):1–13. https://doi.org/10.1186/s12934-018-0929-4
García-Estrada C, Ullán RV, Albillos SM, Fernández-Bodega MÁ, Durek P, von Döhren H, Martín JF (2011) A single cluster of coregulated genes encodes the biosynthesis of the mycotoxins roquefortine C and meleagrin in Penicillium chrysogenum. Chem Biol 18(11):1499–1512. https://doi.org/10.1016/J.CHEMBIOL.2011.08.012
Gassel S, Breitenbach J, Sandmann G (2014) Genetic engineering of the complete carotenoid pathway towards enhanced astaxanthin formation in Xanthophyllomyces dendrorhous starting from a high-yield mutant. Appl Microbiol Biotechnol 98(1):345–350. https://doi.org/10.1007/S00253-013-5358-Z
Gaucher GM, Shepherd MG (1968) Isolation of orsellinic acid synthase. Biochem Biophys Res Commun 32(4):664–671. https://doi.org/10.1016/0006-291X(68)90290-8
Gaude N, Bortfeld S, Erban A, Kopka J, Krajinski F (2015) Symbiosis dependent accumulation of primary metabolites in arbuscule-containing cells. BMC Plant Biol 15(1):234. https://doi.org/10.1186/s12870-015-0601-7
Gerhards N, Neubauer L, Tudzynski P, Li S-M (1950) Biosynthetic pathways of ergot alkaloids. Toxins 6:3281–3295. https://doi.org/10.3390/toxins6123281
Gmoser R, Ferreira JA, Lennartsson PR, Taherzadeh MJ (2017) Filamentous ascomycetes fungi as a source of natural pigments. Fungal Biol Biotechnol 4(1):4. https://doi.org/10.1186/s40694-017-0033-2
Gómez BL, Nosanchuk JD (2003) Melanin and fungi. Curr Opin Infect Dis 16(2):91–96. https://doi.org/10.1097/00001432-200304000-00005
Gupta VK, Rodriguez-Couto S (2017) New and future developments in microbial biotechnology and bioengineering: Penicillum system properties and applications. In: New and future developments in microbial biotechnology and bioengineering: Penicillium system properties and applications. Elsevier. https://doi.org/10.1016/C2014-0-00305-X
Guzmán-Chávez F, Zwahlen RD, Bovenberg RAL, Driessen AJM (2018) Engineering of the filamentous fungus penicillium chrysogenumas cell factory for natural products. Front Microbiol 9(NOV):1–25. https://doi.org/10.3389/fmicb.2018.02768
Hanson JR (2008) The chemistry of fungi. https://doi.org/10.1039/9781847558329
Hartmann T (2007) From waste products to ecochemicals: fifty years research of plant secondary metabolism. Phytochemistry 68(22–24):2831–2846. https://doi.org/10.1016/J.PHYTOCHEM.2007.09.017
Hoffmeister D, Keller NP (2007) Natural products of filamentous fungi: enzymes, genes, and their regulation. Nat Prod Rep 24(2):393–416. https://doi.org/10.1039/b603084j. Epub 2006 Dec 20
Iacovelli R, Bovenberg RAL, Driessen AJM (2021) Nonribosomal peptide synthetases and their biotechnological potential in Penicillium rubens. J Ind Microbiol Biotechnol 48(7–8). https://doi.org/10.1093/jimb/kuab045
Izoré T, Candace Ho YT, Kaczmarski JA, Gavriilidou A, Chow KH, Steer DL, Goode RJA, Schittenhelm RB, Tailhades J, Tosin M, Challis GL, Krenske EH, Ziemert N, Jackson CJ, Cryle MJ (2021) Structures of a non-ribosomal peptide synthetase condensation domain suggest the basis of substrate selectivity. Nat Commun 12(1):1–14. https://doi.org/10.1038/s41467-021-22623-0
Javidpour P, Das A, Khosla C, Tsai S-C (2011) Structural and biochemical studies of the hedamycin type II polyketide ketoreductase (Hed KR): molecular basis of stereo- and regiospecificities. Biochemistry 50(34):7426–7439. https://doi.org/10.1021/bi2006866
Kała K, Kryczyk-Poprawa A, Rzewińska A, Muszyńska B (2020) Fruiting bodies of selected edible mushrooms as a potential source of lovastatin. Eur Food Res Technol 246(4):713–722. https://doi.org/10.1007/s00217-020-03435-w
Kalra R, Conlan XA, Goel M (2020) Fungi as a potential source of pigments: harnessing filamentous fungi. Front Chem 8. https://doi.org/10.3389/fchem.2020.00369
Kaneko A, Morishita Y, Tsukada K, Taniguchi T, Asai T (2019) Post-genomic approach based discovery of alkylresorcinols from a cricket-associated fungus, Penicillium soppi. Org Biomol Chem 17(21):5239–5243. https://doi.org/10.1039/C9OB00807A
Keller NP (2019) Fungal secondary metabolism: regulation, function and drug discovery. Nat Rev Microbiol 17(3):167–180. https://doi.org/10.1038/s41579-018-0121-1
Keller NP, Hohn TM (1997) Metabolic pathway gene clusters in filamentous fungi. Fungal Genet Biol 21:17–29
Keller NP, Turner G, Bennett JW (2005) Fungal secondary metabolism – from biochemistry to genomics. Nat Rev Microbiol 3(12):937–947. https://doi.org/10.1038/NRMICRO1286
Khyade MS, Kasote DM, Vaikos NP (2014) Alstonia scholaris (L.) R. Br. and Alstonia macrophylla Wall. ex G. Don: a comparative review on traditional uses, phytochemistry and pharmacology. J Ethnopharmacol 153(1):1–18. https://doi.org/10.1016/J.JEP.2014.01.025
Kinghorn AD (2020) Progress in the chemistry of organic natural products 111. In: Falk H, Gibbons S, Kobayashi J, Asakawa Y, Liu J-K (eds) , vol 111. Springer. https://doi.org/10.1007/978-3-030-37865-3
Kjærbølling I, Mortensen UH, Vesth T, Andersen MR (2019) Strategies to establish the link between biosynthetic gene clusters and secondary metabolites. Fungal Genet Biol 130:107–121. https://doi.org/10.1016/j.fgb.2019.06.001
Králová M, Frébortová J, Pěnčík A, Frébort I (2021) Overexpression of Trp-related genes in Claviceps purpurea leading to increased ergot alkaloid production. New Biotechnol 61:69–79. https://doi.org/10.1016/J.NBT.2020.11.003
Le Govic Y, Papon N, Le Gal S, Bouchara JP, Vandeputte P (2019) Non-ribosomal peptide synthetase gene clusters in the human pathogenic fungus Scedosporium apiospermum. Front Microbiol 10(September):1–14. https://doi.org/10.3389/fmicb.2019.02062
Lee SL, Floss HG, Heinstein P (1976) Purification and properties of dimethylallylpyrophosphate: tryptopharm dimethylallyl transferase, the first enzyme of ergot alkaloid biosynthesis in Claviceps. sp. SD 58. Arch Biochem Biophys 177(1):84–94. https://doi.org/10.1016/0003-9861(76)90418-5
Li SM (2009) Evolution of aromatic prenyltransferases in the biosynthesis of indole derivatives. Phytochemistry 70(15–16):1746–1757. https://doi.org/10.1016/J.PHYTOCHEM.2009.03.019
Li K, Gustafson KR (2021) Sesterterpenoids: chemistry, biology, and biosynthesis. Nat Prod Rep 38(7):1251–1281. https://doi.org/10.1039/D0NP00070A
Li Z-J, Wang Y-Z, Wang L-R, Shi T-Q, Sun X-M, Huang H (2021) Advanced strategies for the synthesis of terpenoids in Yarrowia lipolytica. J Agric Food Chem 69(8):2367–2381. https://doi.org/10.1021/acs.jafc.1c00350
Liao P, Hemmerlin A, Bach TJ, Chye M-L (2016) The potential of the mevalonate pathway for enhanced isoprenoid production. Biotechnol Adv 34(5):697–713. https://doi.org/10.1016/j.biotechadv.2016.03.005
Liu M, Panaccione DG, Schardl CL (2009) Phylogenetic analyses reveal monophyletic origin of the ergot alkaloid gene dmaW in fungi. Evol Bioinformatics Online 5(5):15–30. https://doi.org/10.4137/EBO.S2633
Lovenberg W, Weissbach H, Udenfriend S (1962) Aromatic l-amino acid decarboxylase. J Biol Chem 237(1):89–93. https://doi.org/10.1016/S0021-9258(18)81366-7
Luk LYP, Tanner ME (2009) Mechanism of dimethylallyltryptophan synthase: evidence for a dimethylallyl cation intermediate in an aromatic prenyltransferase reaction. J Am Chem Soc 131(39):13932–13933. https://doi.org/10.1021/JA906485U/SUPPL_FILE/JA906485U_SI_001.PDF
Manoharan G, Sairam T, Thangamani R, Ramakrishnan D, Tiwari MK, Lee J-K, Marimuthu J (2019) Identification and characterization of type III polyketide synthase genes from culturable endophytes of ethnomedicinal plants. Enzym Microb Technol 131:109396. https://doi.org/10.1016/j.enzmictec.2019.109396
Martín J-F, García-Estrada C, Zeilinger S (2014) In: Martín J-F, García-Estrada C, Zeilinger S (eds) Biosynthesis and molecular genetics of fungal secondary metabolites. Springer, New York. https://doi.org/10.1007/978-1-4939-1191-2
Martínez-Núñez MA, López VEL, y. (2016) Nonribosomal peptides synthetases and their applications in industry. Sustain Chem Process 4(1):1–8. https://doi.org/10.1186/s40508-016-0057-6
Masi M, Dasari R, Evidente A, Mathieu V, Kornienko A (2019) Chemistry and biology of ophiobolin A and its congeners. Bioorg Med Chem Lett 29(7):859–869. https://doi.org/10.1016/J.BMCL.2019.02.007
Matuschek M, Wallwey C, Xie X, Li SM (2011) New insights into ergot alkaloid biosynthesis in Claviceps purpurea: an agroclavine synthase EasG catalyses, via a non-enzymatic adduct with reduced glutathione, the conversion of chanoclavine-I aldehyde to agroclavine. Org Biomol Chem 9(11):4328–4335. https://doi.org/10.1039/C0OB01215G
Matuschek M, Wallwey C, Wollinsky B, Xie X, Li SM (2012) In vitro conversion of chanoclavine-I aldehyde to the stereoisomers festuclavine and pyroclavine controlled by the second reduction step. RSC Adv 2(9):3662–3669. https://doi.org/10.1039/C2RA20104F
McGuire JM, Bunch RL, Anderson RC, Boaz HE, Flynn EH, Powell HM (1952) Ilotycin, a new antibiotic. Antibiot Chemother 2:281–283
Metzger U, Schall C, Zocher G, Unsöld I, Stec E, Li SM, Heide L, Stehle T (2009) The structure of dimethylallyl tryptophan synthase reveals a common architecture of aromatic prenyltransferases in fungi and bacteria. Proc Natl Acad Sci U S A 106(34):14309. https://doi.org/10.1073/PNAS.0904897106
Miller BR, Drake EJ, Shi C, Aldrich CC, Gulick AM (2016) Structures of a nonribosomal peptide synthetase module bound to Mbt H-like proteins support a highly dynamic domain architecture. J Biol Chem 291(43):22559–22571. https://doi.org/10.1074/jbc.M116.746297
Mulder KCL, Mulinari F, Franco OL, Soares MSF, Magalhães BS, Parachin NS (2015) Lovastatin production: from molecular basis to industrial process optimization. Biotechnol Adv 33(6):648–665. https://doi.org/10.1016/j.biotechadv.2015.04.001
Mussagy CU, Winterburn J, Santos-Ebinuma VC, Pereira JFB (2019) Production and extraction of carotenoids produced by microorganisms. Appl Microbiol Biotechnol 103(3):1095–1114. https://doi.org/10.1007/s00253-018-9557-5
Netzker T, Fischer J, Weber J, Mattern DJ, König CC, Valiante V, Schroeckh V, Brakhage AA (2015) Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters. Front Microbiol 6. https://doi.org/10.3389/fmicb.2015.00299
Niu X, Thaochan N, Hu Q (2020) Diversity of linear non-ribosomal peptide in biocontrol fungi. Journal of Fungi 6(2). https://doi.org/10.3390/jof6020061
Novak B, Lopes Hasuda A, Ghanbari M, Mayumi Maruo V, Bracarense APFRL, Neves M, Emsenhuber C, Wein S, Oswald IP, Pinton P, Schatzmayr D (2021) Effects of Fusarium metabolites beauvericin and enniatins alone or in mixture with deoxynivalenol on weaning piglets. Food Chem Toxicol 158:112719. https://doi.org/10.1016/j.fct.2021.112719
von Nussbaum F (2003) Stephacidin B-A new stage of complexity within prenylated indole alkaloids from fungi. Angew Chem Int Ed Engl 42(27):3068–3071. https://doi.org/10.1002/ANIE.200301646
Oide S, Turgeon BG (2020) Natural roles of nonribosomal peptide metabolites in fungi. Mycoscience 61(3):101–110. https://doi.org/10.1016/j.myc.2020.03.001
Okada M, Matsuda Y, Mitsuhashi T, Hoshino S, Mori T, Nakagawa K, Quan Z, Qin B, Zhang H, Hayashi F, Kawaide H, Abe I (2016) Genome-based discovery of an unprecedented cyclization mode in fungal Sesterterpenoid biosynthesis. J Am Chem Soc 138(31):10011–10018. https://doi.org/10.1021/jacs.6b05799
Oudin A, Courtois M, Rideau M, Clastre M (2007) The iridoid pathway in Catharanthus roseus alkaloid biosynthesis. Phytochem Rev 6(2–3):259–276. https://doi.org/10.1007/S11101-006-9054-9
Pallarés N, Righetti L, Generotti S, Cavanna D, Ferrer E, Dall’Asta, C., & Suman, M. (2020) Investigating the in vitro catabolic fate of Enniatin B in a human gastrointestinal and colonic model. Food Chem Toxicol 137(January):111166. https://doi.org/10.1016/j.fct.2020.111166
Petersen AB, Rønnest MH, Larsen TO, Clausen MH (2014) The chemistry of Griseofulvin. Chem Rev 114(24):12088–12107. https://doi.org/10.1021/cr400368e
Ramakrishnan D, Tiwari MK, Manoharan G, Sairam T, Thangamani R, Lee J-K, Marimuthu J (2018) Molecular characterization of two alkylresorcylic acid synthases from Sordariomycetes fungi. Enzym Microb Technol 115:16–22. https://doi.org/10.1016/j.enzmictec.2018.04.006
Rosazza JP (1984) Fungal metabolites. Vol II by W B Turner and D C Aldridge Academic Press. J Pharmaceut Sci 73(12):1878–1878. https://doi.org/10.1002/JPS.2600731270
Sakhkhari K, Surekha M, Reddy SM (2019) Cytochalasins : incidence and biological activities, India
Schmidt-Dannert C (2015) Biosynthesis of terpenoid natural products in fungi (pp. 19–61). https://doi.org/10.1007/10_2014_283
Schuemann J, Hertweck C (2009) Biosynthesis of fungal polyketides. In: Physiology and genetics. Springer, Berlin, pp 331–351. https://doi.org/10.1007/978-3-642-00286-1_16
Shalaby S, Horwitz BA (2015) Plant phenolic compounds and oxidative stress: integrated signals in fungal–plant interactions. Curr Genet 61(3):347–357. https://doi.org/10.1007/s00294-014-0458-6
Shimizu T, Kinoshita H, Ishihara S, Sakai K, Nagai S, Nihira T (2005) Polyketide synthase gene responsible for citrinin biosynthesis in Monascus purpureus. Appl Environ Microbiol 71(7):3453–3457. https://doi.org/10.1128/AEM.71.7.3453-3457.2005
Simpson TJ, Cox RJ (2012) Polyketides in fungi. Nat Prod Chem Biol 143–161. https://doi.org/10.1002/9781118391815.CH6
Skellam E (2022) Biosynthesis of fungal polyketides by collaborating and trans-acting enzymes. Nat Prod Rep. https://doi.org/10.1039/D1NP00056J
Steffan N, Li SM (2009) Increasing structure diversity of prenylated diketopiperazine derivatives by using a 4-dimethylallyltryptophan synthase. Arch Microbiol 191(5):461–466. https://doi.org/10.1007/S00203-009-0467-X
Steffan N, Unsöld IA, Li SM (2007) Chemoenzymatic synthesis of prenylated indole derivatives by using a 4-dimethylallyltryptophan synthase from Aspergillus fumigatus. Chembiochem Eur J Chem Biol 8(11):1298–1307. https://doi.org/10.1002/CBIC.200700107
Sumarah MW, Miller JD, Blackwell BA (2005) Isolation and metabolite production by Penicillium roqueforti, P. paneum and P. crustosum isolated in Canada. Mycopathologia 159(4):571–577. https://doi.org/10.1007/S11046-005-5257-7
Süssmuth R, Müller J, Von Döhren H, Molnár I (2011) Fungal cyclooligomer depsipeptides: from classical biochemistry to combinatorial biosynthesis. Nat Prod Rep 28(1):99–124. https://doi.org/10.1039/c001463j
Thirumurugan D, Cholarajan A, Raja SSS, Vijayakumar R (2018) An introductory chapter: secondary metabolites. In: Vijayakumar R, Raja SSS (eds) Secondary metabolites – sources and applications. INTECH. https://doi.org/10.5772/intechopen.79766
Tudzynski P, Hölter K, Correia T, Arntz C, Grammel N, Keller U (1999) Evidence for an ergot alkaloid gene cluster in Claviceps purpurea. Mol Gen Genet MGG 261(1):133–141. https://doi.org/10.1007/S004380050950
Tudzynski P, Correia T, Keller U (2001) Biotechnology and genetics of ergot alkaloids. Appl Microbiol Biotechnol 57(5–6):593–605. https://doi.org/10.1007/S002530100801
Turner WB, Aldridge DC (1971) Fungal metabolites. https://books.google.com/books/about/Fungal_Metabolites.html?hl=pt-PT & id=y7fwAAAAMAAJ
Ulusoy M, Aslıyüce S, Keskin N, Denizli A (2022) Beauvericin purification from fungal strain using molecularly imprinted cryogels. Process Biochem 113(March 2021):185–193. https://doi.org/10.1016/j.procbio.2021.12.031
Unsöld IA, Li SM (2005) Overproduction, purification and characterization of FgaPT2, a dimethylallyltryptophan synthase from Aspergillus fumigatus. Microbiology 151(Pt 5):1499–1505. https://doi.org/10.1099/MIC.0.27759-0
Wallwey C, Matuschek M, Xie XL, Li SM (2010) Ergot alkaloid biosynthesis in Aspergillus fumigatus: conversion of chanoclavine-I aldehyde to festuclavine by the festuclavine synthase FgaFS in the presence of the old yellow enzyme FgaOx3. Org Biomol Chem 8(15):3500–3508. https://doi.org/10.1039/C003823G
Wang X, Gong X, Li P, Lai D, Zhou L (2018) Structural diversity and biological activities of cyclic depsipeptides from fungi. Molecules 23(1). https://doi.org/10.3390/molecules23010169
Wang ZW, Zhang JP, Wei QH, Chen L, Lin YL, Wang YL, An T, Wang XJ (2021) Rupestrisine A and B, two novel dimeric indole alkaloids from Alstonia rupestris. Tetrahedron Lett 87:153525. https://doi.org/10.1016/J.TETLET.2021.153525
Watanabe A, Ebizuka Y (2002) A novel hexaketide naphthalene synthesized by a chimeric polyketide synthase composed of fungal pentaketide and heptaketide synthases. Tetrahedron Lett 43(5):843–846. https://doi.org/10.1016/S0040-4039(01)02251-1
Watanabe A, Ono Y, Fujii I, Sankawa U, Mayorga ME, Timberlake WE, Ebizuka Y (1998) Product identification of polyketide synthase coded by Aspergillus nidulans wA gene. Tetrahedron Lett 39(42):7733–7736. https://doi.org/10.1016/S0040-4039(98)01685-2
Webster J, Weber R (2007) Introduction to fungi. Cambridge University Press
Wiemann P, Keller NP (2014) Strategies for mining fungal natural products. J Ind Microbiol Biotechnol 41(2):301–313. https://doi.org/10.1007/S10295-013-1366-3
Xie X, Wallwey C, Matuschek M, Steinbach K, Li SM (2011) Formyl migration product of chanoclavine-I aldehyde in the presence of the old yellow enzyme FgaOx3 from Aspergillus fumigatus: a NMR structure elucidation. Magn Reson Chem MRC 49(10):678–681. https://doi.org/10.1002/MRC.2796
Xu W, Gavia DJ, Tang Y (2014) Biosynthesis of fungal indole alkaloids. Nat Prod Rep 31(10):1474–1487. https://doi.org/10.1039/C4NP00073K
Yaegashi J, Oakley BR, Wang CCC (2014) Recent advances in genome mining of secondary metabolite biosynthetic gene clusters and the development of heterologous expression systems in Aspergillus nidulans. J Ind Microbiol Biotechnol 41(2):433–442. https://doi.org/10.1007/S10295-013-1386-Z
Yan X, Zhang B, Tian W, Dai Q, Zheng X, Hu K, Liu X, Deng Z, Qu X (2018) Puromycin A, B and C, cryptic nucleosides identified from Streptomyces alboniger NRRL B-1832 by PPtase-based activation. Synth Syst Biotechnol 3(1):76–80. https://doi.org/10.1016/j.synbio.2018.02.001
Yu HF, Ding CF, Zhang LC, Wei X, Cheng GG, Liu YP, Zhang RP, Luo XD (2021) Alstoscholarisine K, an antimicrobial indole from Gall-induced leaves of Alstonia scholaris. Org Lett 23(15):5782–5786. https://doi.org/10.1021/ACS.ORGLETT.1C01942/SUPPL_FILE/OL1C01942_SI_002.ZIP
Zhao W-Y, Yi J, Chang Y-B, Sun C-P, Ma X-C (2022) Recent studies on terpenoids in Aspergillus fungi: chemical diversity, biosynthesis, and bioactivity. Phytochemistry 193:113011. https://doi.org/10.1016/j.phytochem.2021.113011
Zheng L, Yang Y, Wang H, Fan A, Zhang L, Li S-M (2020) Ustethylin biosynthesis implies phenethyl derivative formation in Aspergillus ustus Figure 1. Origins of ethyl groups in phenethyl-containing natural products. Org Lett 2022. https://doi.org/10.1021/acs.orglett.0c02719
Acknowledgments
FCT, Portugal for financial support through national funds FCT/MCTES to the CIMO (UIDB/00690/2020), and the Bio Based Industries Joint Undertaking (JU) under the grant agreement No 888003 UP4HEALTH Project (H2020-BBI-JTI-2019), whom the author F.S. Reis thanks for her contract.
L. Barros thank the national funding by FCT, P.I., through the institutional scientific employment program-contract for her contract. T. Oludemi and T.C.S.P. Pires thank the MICINN for their Juan de la Cierva Formación contract (FJC2019-042549-I and FJC2020-045405-I, respectively). The authors also thank the FEDER-Interreg España-Portugal programme through the project TRANSCoLAB 0612_TRANS_CO_LAB_2_P.
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Pascoalino, L.A., Pires, T.C.S.P., Taofiq, O., Ferreira, I.C.F.R., Barros, L., Reis, F.S. (2023). Biochemistry of Secondary Metabolism of Fungi. In: Carocho, M., Heleno, S.A., Barros, L. (eds) Natural Secondary Metabolites. Springer, Cham. https://doi.org/10.1007/978-3-031-18587-8_13
Download citation
DOI: https://doi.org/10.1007/978-3-031-18587-8_13
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-18586-1
Online ISBN: 978-3-031-18587-8
eBook Packages: Chemistry and Materials ScienceChemistry and Material Science (R0)