Translating biosynthetic gene clusters into fungal armor and weaponry

Abstract

Filamentous fungi are renowned for the production of a diverse array of secondary metabolites (SMs) where the genetic material required for synthesis of a SM is typically arrayed in a biosynthetic gene cluster (BGC). These natural products are valued for their bioactive properties stemming from their functions in fungal biology, key among those protection from abiotic and biotic stress and establishment of a secure niche. The producing fungus must not only avoid self-harm from endogenous SMs but also deliver specific SMs at the right time to the right tissue requiring biochemical aid. This review highlights functions of BGCs beyond the enzymatic assembly of SMs, considering the timing and location of SM production and other proteins in the clusters that control SM activity. Specifically, self-protection is provided by both BGC-encoded mechanisms and non-BGC subcellular containment of toxic SM precursors; delivery and timing is orchestrated through cellular trafficking patterns and stress- and developmental-responsive transcriptional programs.

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Figure 1: Fungal BGCs can contain genes encoding one or more self-protective devices.

KIM CAESER/NATURE PUBLISHING GROUP

Figure 2: Subcellular trafficking models for biosynthesis of aflatoxin, penicillin and trichothecene.

KIM CAESAR/NATURE PUBLISHING GROUP

Figure 3: A transcriptional conduit from LaeA to BrlA regulates production of spore secondary metabolites.

KIM CAESER/NATURE PUBLISHING GROUP

References

  1. 1

    Demain, A.L. & Fang, A. The natural functions of secondary metabolites. Adv. Biochem. Eng. Biotechnol. 69, 1–39 (2000).

    CAS  PubMed  Google Scholar 

  2. 2

    Rohlfs, M. & Churchill, A.C. Fungal secondary metabolites as modulators of interactions with insects and other arthropods. Fungal Genet. Biol. 48, 23–34 (2011).

    Article  CAS  Google Scholar 

  3. 3

    Stergiopoulos, I., Collemare, J., Mehrabi, R. & De Wit, P.J. Phytotoxic secondary metabolites and peptides produced by plant pathogenic Dothideomycete fungi. FEMS Microbiol. Rev. 37, 67–93 (2013).

    Article  CAS  Google Scholar 

  4. 4

    Dagenais, T.R. & Keller, N.P. Pathogenesis of Aspergillus fumigatus in invasive aspergillosis. Clin. Microbiol. Rev. 22, 447–465 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 5

    Johnson, J.R., Bruce, W.F. & Dutcher, J.D. Gliotoxin, the antibiotic principle of Gliocladium fimbriatum. I. Production, physical and biological properties. J. Am. Chem. Soc. 65, 2005–2009 (1943).

    Article  CAS  Google Scholar 

  6. 6

    Brian, P.W. & Hemming, H.G. Gliotoxin, a fungistatic metabolic product of Trichoderma viride. Ann. Appl. Biol. 32, 214–220 (1945).

    Article  CAS  Google Scholar 

  7. 7

    Carberry, S. et al. Gliotoxin effects on fungal growth: mechanisms and exploitation. Fungal Genet. Biol. 49, 302–312 (2012).

    Article  CAS  Google Scholar 

  8. 8

    Vigushin, D.M. et al. Gliotoxin is a dual inhibitor of farnesyltransferase and geranylgeranyltransferase I with antitumor activity against breast cancer in vivo. Med. Oncol. 21, 21–30 (2004).

    Article  CAS  Google Scholar 

  9. 9

    Reece, K.M. et al. Epidithiodiketopiperazines (ETPs) exhibit in vitro antiangiogenic and in vivo antitumor activity by disrupting the HIF-1a/p300 complex in a preclinical model of prostate cancer. Mol. Cancer 13, 91 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. 10

    Nyilasi, I. et al. Susceptibility of clinically important dermatophytes against statins and different statin-antifungal combinations. Med. Mycol. 52, 140–148 (2014).

    CAS  PubMed  Google Scholar 

  11. 11

    Haughan, P.A., Chance, M.L. & Goad, L.J. Synergism in vitro of lovastatin and miconazole as anti-leishmanial agents. Biochem. Pharmacol. 44, 2199–2206 (1992).

    Article  CAS  Google Scholar 

  12. 12

    Desoubeaux, G. et al. Successful treatment with fumagillin of the first pediatric case of digestive microsporidiosis in a liver-kidney transplant. Transpl. Infect. Dis. 15, E250–E259 (2013).

    Article  CAS  Google Scholar 

  13. 13

    Maggi, M. et al. Effects of the organic acids produced by a lactic acid bacterium in Apis mellifera colony development, Nosema ceranae control and fumagillin efficiency. Vet. Microbiol. 167, 474–483 (2013).

    Article  CAS  Google Scholar 

  14. 14

    Howland, R.H. Aspergillus, angiogenesis, and obesity: the story behind beloranib. J. Psychosoc. Nurs. Ment. Health Serv. 53, 13–16 (2015).

    PubMed  Google Scholar 

  15. 15

    Kornienko, A. et al. Toward a cancer drug of fungal origin. Med. Res. Rev. doi:10.1002/med.21348 (8 April 2015).

  16. 16

    Viaud, M.C., Balhadere, P.V. & Talbot, N.J. A Magnaporthe grisea cyclophilin acts as a virulence determinant during plant infection. Plant Cell 14, 917–930 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. 17

    Chamilos, G., Lewis, R.E. & Kontoyiannis, D.P. Lovastatin has significant activity against zygomycetes and interacts synergistically with voriconazole. Antimicrob. Agents Chemother. 50, 96–103 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. 18

    Nyilasi, I. et al. Susceptibility of clinically important dermatophytes against statins and different statin-antifungal combinations. Med. Mycol. 52, 140–148 (2014).

    CAS  PubMed  Google Scholar 

  19. 19

    Abe, Y. et al. Effect of increased dosage of the ML-236B (compactin) biosynthetic gene cluster on ML-236B production in Penicillium citrinum. Mol. Genet. Genomics 268, 130–137 (2002).

    Article  CAS  Google Scholar 

  20. 20

    Wiemann, P. et al. Prototype of an intertwined secondary-metabolite supercluster. Proc. Natl. Acad. Sci. USA 110, 17065–17070 (2013).

    Article  CAS  Google Scholar 

  21. 21

    Bushley, K.E. et al. The genome of Tolypocladium inflatum: evolution, organization, and expression of the cyclosporin biosynthetic gene cluster. PLoS Genet. 9, e1003496 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. 22

    Regueira, T.B. et al. Molecular basis for mycophenolic acid biosynthesis in Penicillium brevicompactum. Appl. Environ. Microbiol. 77, 3035–3043 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. 23

    Scharf, D.H. et al. Transannular disulfide formation in gliotoxin biosynthesis and its role in self-resistance of the human pathogen Aspergillus fumigatus. J. Am. Chem. Soc. 132, 10136–10141 (2010).

    Article  CAS  Google Scholar 

  24. 24

    Dolan, S.K., O'Keeffe, G., Jones, G.W. & Doyle, S. Resistance is not futile: gliotoxin biosynthesis, functionality and utility. Trends Microbiol. 23, 419–428 (2015).

    Article  CAS  Google Scholar 

  25. 25

    Kimura, M. et al. Trichothecene 3-O-acetyltransferase protects both the producing organism and transformed yeast from related mycotoxins. Cloning and characterization of Tri101. J. Biol. Chem. 273, 1654–1661 (1998).

    Article  CAS  Google Scholar 

  26. 26

    Ohsato, S. et al. Transgenic rice plants expressing trichothecene 3-O-acetyltransferase show resistance to the Fusarium phytotoxin deoxynivalenol. Plant Cell Rep. 26, 531–538 (2007).

    Article  CAS  Google Scholar 

  27. 27

    Alexander, N.J., McCormick, S.P. & Hohn, T.M. TRI12, a trichothecene efflux pump from Fusarium sporotrichioides: gene isolation and expression in yeast. Mol. Gen. Genet. 261, 977–984 (1999).

    Article  CAS  Google Scholar 

  28. 28

    Andersen, M.R. et al. Accurate prediction of secondary metabolite gene clusters in filamentous fungi. Proc. Natl. Acad. Sci. USA 110, E99–E107 (2013).

    Article  Google Scholar 

  29. 29

    Gardiner, D.M., Jarvis, R.S. & Howlett, B.J. The ABC transporter gene in the sirodesmin biosynthetic gene cluster of Leptosphaeria maculans is not essential for sirodesmin production but facilitates self-protection. Fungal Genet. Biol. 42, 257–263 (2005).

    Article  CAS  Google Scholar 

  30. 30

    Menke, J., Dong, Y. & Kistler, H.C. Fusarium graminearum Tri12p influences virulence to wheat and trichothecene accumulation. Mol. Plant Microbe Interact. 25, 1408–1418 (2012).

    Article  CAS  Google Scholar 

  31. 31

    Wiemann, P. et al. Biosynthesis of the red pigment bikaverin in Fusarium fujikuroi: genes, their function and regulation. Mol. Microbiol. 72, 931–946 (2009).

    Article  CAS  Google Scholar 

  32. 32

    Chang, P.K., Yu, J. & Yu, J.H. aflT, a MFS transporter-encoding gene located in the aflatoxin gene cluster, does not have a significant role in aflatoxin secretion. Fungal Genet. Biol. 41, 911–920 (2004).

    Article  CAS  Google Scholar 

  33. 33

    Amnuaykanjanasin, A. & Daub, M.E. The ABC transporter ATR1 is necessary for efflux of the toxin cercosporin in the fungus Cercospora nicotianae. Fungal Genet. Biol. 46, 146–158 (2009).

    Article  CAS  Google Scholar 

  34. 34

    Lee, S., Son, H., Lee, J., Lee, Y.R. & Lee, Y.W. A putative ABC transporter gene, ZRA1, is required for zearalenone production in Gibberella zeae. Curr. Genet. 57, 343–351 (2011).

    Article  CAS  Google Scholar 

  35. 35

    Perlin, M.H., Andrews, J. & Toh, S.S. Essential letters in the fungal alphabet: ABC and MFS transporters and their roles in survival and pathogenicity. Adv. Genet. 85, 201–253 (2014).

    Article  CAS  Google Scholar 

  36. 36

    Beseli, A., Amnuaykanjanasin, A., Herrero, S., Thomas, E. & Daub, M.E. Membrane transporters in self resistance of Cercospora nicotianae to the photoactivated toxin cercosporin. Curr. Genet. http://dx.doi.org/10.1007/s00294-015-0486-x (11 April 2015).

  37. 37

    Dubey, M.K., Jensen, D.F. & Karlsson, M. An ATP-binding cassette pleiotropic drug transporter protein is required for xenobiotic tolerance and antagonism in the fungal biocontrol agent Clonostachys rosea. Mol. Plant Microbe Interact. 27, 725–732 (2014).

    Article  CAS  Google Scholar 

  38. 38

    Kistler, H.C. & Broz, K. Cellular compartmentalization of secondary metabolism. Front. Microbiol. 6, 68 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  39. 39

    Lim, F.Y. & Keller, N.P. Spatial and temporal control of fungal natural product synthesis. Nat. Prod. Rep. 31, 1277–1286 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. 40

    Fernández-Aguado, M., Ullan, R.V., Teijeira, F., Rodriguez-Castro, R. & Martin, J.F. The transport of phenylacetic acid across the peroxisomal membrane is mediated by the PaaT protein in Penicillium chrysogenum. Appl. Microbiol. Biotechnol. 97, 3073–3084 (2013).

    Article  CAS  Google Scholar 

  41. 41

    Herr, A. & Fischer, R. Improvement of Aspergillus nidulans penicillin production by targeting AcvA to peroxisomes. Metab. Eng. 25, 131–139 (2014).

    Article  CAS  Google Scholar 

  42. 42

    Steinberg, G. Endocytosis and early endosome motility in filamentous fungi. Curr. Opin. Microbiol. 20, 10–18 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. 43

    Fernández-Aguado, M., Teijeira, F., Martin, J.F. & Ullan, R.V. A vacuolar membrane protein affects drastically the biosynthesis of the ACV tripeptide and the b-lactam pathway of Penicillium chrysogenum. Appl. Microbiol. Biotechnol. 97, 795–808 (2013).

    Article  CAS  Google Scholar 

  44. 44

    Chanda, A. et al. A key role for vesicles in fungal secondary metabolism. Proc. Natl. Acad. Sci. USA 106, 19533–19538 (2009).

    Article  Google Scholar 

  45. 45

    Banerjee, S. et al. Quantitative acoustic contrast tomography reveals unique multiscale physical fluctuations during aflatoxin synthesis in Aspergillus parasiticus. Fungal Genet. Biol. 73, 61–68 (2014).

    Article  CAS  Google Scholar 

  46. 46

    Hong, S.Y., Roze, L.V. & Linz, J.E. Oxidative stress-related transcription factors in the regulation of secondary metabolism. Toxins (Basel) 5, 683–702 (2013).

    Article  CAS  Google Scholar 

  47. 47

    Montibus, M., Pinson-Gadais, L., Richard-Forget, F., Barreau, C. & Ponts, N. Coupling of transcriptional response to oxidative stress and secondary metabolism regulation in filamentous fungi. Crit. Rev. Microbiol. 41, 295–308 (2015).

    Article  CAS  Google Scholar 

  48. 48

    Rodrigues-Pousada, C., Menezes, R.A. & Pimentel, C. The Yap family and its role in stress response. Yeast 27, 245–258 (2010).

    Article  CAS  Google Scholar 

  49. 49

    Netzker, T. et al. Microbial communication leading to the activation of silent fungal secondary metabolite gene clusters. Front. Microbiol. 6, 299 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  50. 50

    Rohlfs, M. Fungal secondary metabolite dynamics in fungus-grazer interactions: novel insights and unanswered questions. Front. Microbiol. 5, 788 (2014).

    PubMed  Google Scholar 

  51. 51

    Zheng, H. et al. Redox metabolites signal polymicrobial biofilm development via the NapA oxidative stress cascade in Aspergillus. Curr. Biol. 25, 29–37 (2015).

    Article  CAS  Google Scholar 

  52. 52

    Yin, W.B. et al. An Aspergillus nidulans bZIP response pathway hardwired for defensive secondary metabolism operates through aflR. Mol. Microbiol. 83, 1024–1034 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. 53

    Tudzynski, B. Nitrogen regulation of fungal secondary metabolism in fungi. Front. Microbiol. 5, 656 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  54. 54

    Wiemann, P. et al. Perturbations in small molecule synthesis uncovers an iron-responsive secondary metabolite network in Aspergillus fumigatus. Front. Microbiol. 5, 530 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  55. 55

    Brakhage, A.A. Regulation of fungal secondary metabolism. Nat. Rev. Microbiol. 11, 21–32 (2013).

    Article  CAS  Google Scholar 

  56. 56

    Akamatsu, H.O., Chilvers, M.I., Stewart, J.E. & Peever, T.L. Identification and function of a polyketide synthase gene responsible for 1,8-dihydroxynaphthalene-melanin pigment biosynthesis in Ascochyta rabiei. Curr. Genet. 56, 349–360 (2010).

    Article  CAS  Google Scholar 

  57. 57

    Esbelin, J., Mallea, S., Ram, A.F. & Carlin, F. Role of pigmentation in protecting Aspergillus niger conidiospores against pulsed light radiation. Photochem. Photobiol. 89, 758–761 (2013).

    Article  CAS  Google Scholar 

  58. 58

    Imshenetsky, A.A., Lysenko, S.V. & Lach, S.P. Microorganisms of the upper layer of the atmosphere and the protective role of their cell pigments. Life Sci. Space Res. 17, 105–110 (1979).

    Article  CAS  Google Scholar 

  59. 59

    Dadachova, E. et al. Ionizing radiation changes the electronic properties of melanin and enhances the growth of melanized fungi. PLoS ONE 2, e457 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. 60

    Hu, Y. et al. A PKS gene, pks-1, is involved in chaetoglobosin biosynthesis, pigmentation and sporulation in Chaetomium globosum. Sci. China Life Sci. 55, 1100–1108 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. 61

    Islamovic, E. et al. Transcriptome analysis of a Ustilago maydis ust1 deletion mutant uncovers involvement of laccase and polyketide synthase genes in spore development. Mol. Plant Microbe Interact. 28, 42–54 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. 62

    Schindler, D. & Nowrousian, M. The polyketide synthase gene pks4 is essential for sexual development and regulates fruiting body morphology in Sordaria macrospora. Fungal Genet. Biol. 68, 48–59 (2014).

    Article  CAS  Google Scholar 

  63. 63

    Cary, J.W. et al. An Aspergillus flavus secondary metabolic gene cluster containing a hybrid PKS-NRPS is necessary for synthesis of the 2-pyridones, leporins. Fungal Genet. Biol. 81, 88–97 (2015).

    Article  CAS  Google Scholar 

  64. 64

    Cary, J.W. et al. Functional characterization of a veA-dependent polyketide synthase gene in Aspergillus flavus necessary for the synthesis of asparasone, a sclerotium-specific pigment. Fungal Genet. Biol. 64, 25–35 (2014).

    Article  CAS  Google Scholar 

  65. 65

    Forseth, R.R. et al. Homologous NRPS-like gene clusters mediate redundant small-molecule biosynthesis in Aspergillus flavus. Angew. Chem. Int. Edn Engl. 52, 1590–1594 (2013).

    Article  CAS  Google Scholar 

  66. 66

    Calvo, A.M., Wilson, R.A., Bok, J.W. & Keller, N.P. Relationship between secondary metabolism and fungal development. Microbiol. Mol. Biol. Rev. 66, 447–459 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. 67

    Park, H.S. & Yu, J.H. Genetic control of asexual sporulation in filamentous fungi. Curr. Opin. Microbiol. 15, 669–677 (2012).

    Article  CAS  Google Scholar 

  68. 68

    Qin, Y. et al. Penicillium decumbens BrlA extensively regulates secondary metabolism and functionally associates with the expression of cellulase genes. Appl. Microbiol. Biotechnol. 97, 10453–10467 (2013).

    Article  CAS  Google Scholar 

  69. 69

    Mulinti, P. et al. Accumulation of ergot alkaloids during conidiophore development in Aspergillus fumigatus. Curr. Microbiol. 68, 1–5 (2014).

    Article  CAS  Google Scholar 

  70. 70

    Tsai, H.F., Wheeler, M.H., Chang, Y.C. & Kwon-Chung, K.J. A developmentally regulated gene cluster involved in conidial pigment biosynthesis in Aspergillus fumigatus. J. Bacteriol. 181, 6469–6477 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  71. 71

    Berthier, E. et al. Low-volume toolbox for the discovery of immunosuppressive fungal secondary metabolites. PLoS Pathog. 9, e1003289–e1003289 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. 72

    Gauthier, T. et al. Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic to lung cells. PLoS ONE 7, e29906 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. 73

    Lim, F.Y., Ames, B., Walsh, C.T. & Keller, N.P. Co-ordination between BrlA regulation and secretion of the oxidoreductase FmqD directs selective accumulation of fumiquinazoline C to conidial tissues in Aspergillus fumigatus. Cell. Microbiol. 16, 1267–1283 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. 74

    Perrin, R.M. et al. Transcriptional regulation of chemical diversity in Aspergillus fumigatus by LaeA. PLoS Pathog. 3, e50 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. 75

    Roze, L.V., Chanda, A., Wee, J., Awad, D. & Linz, J.E. Stress-related transcription factor AtfB integrates secondary metabolism with oxidative stress response in aspergilli. J. Biol. Chem. 286, 35137–35148 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. 76

    Reverberi, M. et al. Apyap1 affects aflatoxin biosynthesis during Aspergillus parasiticus growth in maize seeds. Food Addit. Contam. 24, 1070–1075 (2007).

    Article  CAS  Google Scholar 

  77. 77

    Yin, W.B. et al. bZIP transcription factors affecting secondary metabolism, sexual development and stress responses in Aspergillus nidulans. Microbiology 159, 77–88 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. 78

    Emri, T. et al. Core oxidative stress response in Aspergillus nidulans. BMC Genomics 16, 478 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. 79

    Wang, X. et al. The bZIP transcription factor PfZipA regulates secondary metabolism and oxidative stress response in the plant endophytic fungus Pestalotiopsis fici. Fungal Genet. Biol. 81, 221–228 (2015).

    Article  CAS  Google Scholar 

  80. 80

    Sekonyela, R. et al. RsmA regulates Aspergillus fumigatus gliotoxin cluster metabolites including Cyclo(L-Phe-L-Ser), a potential new diagnostic marker for invasive aspergillosis. PLoS ONE 8, e62591 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. 81

    Xiao, P., Shin, K.S., Wang, T. & Yu, J.H. Aspergillus fumigatus flbB encodes two basic leucine zipper domain (bZIP) proteins required for proper asexual development and gliotoxin production. Eukaryot. Cell 9, 1711–1723 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. 82

    Montibus, M. et al. The bZIP transcription factor Fgap1 mediates oxidative stress response and trichothecene biosynthesis but not virulence in Fusarium graminearum. PLoS ONE 8, e83377 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. 83

    Van Nguyen, T., Kroger, C., Bonnighausen, J., Schafer, W. & Bormann, J. The ATF/CREB transcription factor Atf1 is essential for full virulence, deoxynivalenol production, and stress tolerance in the cereal pathogen Fusarium graminearum. Mol. Plant Microbe Interact. 26, 1378–1394 (2013).

    Article  CAS  Google Scholar 

  84. 84

    Wagner, D. et al. The bZIP transcription factor MeaB mediates nitrogen metabolite repression at specific loci. Eukaryot. Cell 9, 1588–1601 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. 85

    Amaike, S. et al. The bZIP protein MeaB mediates virulence attributes in Aspergillus flavus. PLoS ONE 8, e74030 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. 86

    Temme, N. et al. BcAtf1, a global regulator, controls various differentiation processes and phytotoxin production in Botrytis cinerea. Mol. Plant Pathol. 13, 704–718 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. 87

    Reverberi, M. et al. Aoyap1 regulates OTA synthesis by controlling cell redox balance in Aspergillus ochraceus. Appl. Microbiol. Biotechnol. 95, 1293–1304 (2012).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by US National Institutes of Health R01 Al065728-09 and R01GM112739-01 to N.P.K.

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Correspondence to Nancy P Keller.

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Keller, N. Translating biosynthetic gene clusters into fungal armor and weaponry. Nat Chem Biol 11, 671–677 (2015). https://doi.org/10.1038/nchembio.1897

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