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A comprehensive catalogue of polyketide synthase gene clusters in lichenizing fungi

  • Natural Products - Mini Review
  • Published:
Journal of Industrial Microbiology & Biotechnology

Abstract

Lichens are fungi that form symbiotic partnerships with algae. Although lichens produce diverse polyketides, difficulties in establishing and maintaining lichen cultures have prohibited detailed studies of their biosynthetic pathways. Creative, albeit non-definitive, methods have been developed to assign function to biosynthetic gene clusters in lieu of techniques such as gene knockout and heterologous expressions that are commonly applied to easily cultivatable organisms. We review a total of 81 completely sequenced polyketide synthase (PKS) genes from lichenizing fungi, comprising to our best efforts all complete and reported PKS genes in lichenizing fungi to date. This review provides an overview of the approaches used to locate and sequence PKS genes in lichen genomes, current approaches to assign function to lichen PKS gene clusters, and what polyketides are proposed to be biosynthesized by these PKS. We conclude with remarks on prospects for genomics-based natural products discovery in lichens. We hope that this review will serve as a guide to ongoing research efforts on polyketide biosynthesis in lichenizing fungi.

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References

  1. Abdel-Hameed M, Bertrand RL, Donald LJ, Sorensen JL (2018) Lichen ketosynthase domains are not responsible for inoperative polyketide synthases in Ascomycota hosts. Biochem Biophys Res Commun. https://doi.org/10.1016/j.bbrc.2018.07.029 (Epub ahead of print)

    Article  PubMed  Google Scholar 

  2. Abdel-Hameed M, Bertrand RL, Piercey-Normore MD, Sorensen JL (2016) Identification of 6-hydroxymellein synthase and accessory genes in the lichen Cladonia uncialis. J Nat Prod 79:1645–1650. https://doi.org/10.1021/acs.jnatprod.6b00257

    Article  CAS  PubMed  Google Scholar 

  3. Abdel-Hameed M, Bertrand RL, Piercey-Normore MD, Sorensen JL (2016) Putative identification of the usnic acid biosynthetic gene cluster by de novo whole-genome sequencing a lichen-forming fungus. Fungal Biol 120:306–316. https://doi.org/10.1016/j.funbio.2015.10.009

    Article  CAS  PubMed  Google Scholar 

  4. Aigle B, Corre C (2012) Waking up Streptomyces secondary metabolism by constitutive expression of activators or genetic disruption of repressors. Methods Enzymol 517:343–366. https://doi.org/10.1016/B978-0-12-404634-4.00017-6

    Article  CAS  PubMed  Google Scholar 

  5. Aigle B, Lautru S, Spiteller D, Dickschat JS, Challis GL, Leblond P, Pernodet JL (2014) Genome mining of Streptomyces ambo faciens. J Ind Microbiol Biotechnol 41:251–263. https://doi.org/10.1007/s10295-013-1379-y

    Article  CAS  PubMed  Google Scholar 

  6. Alberti F, Foster GD, Bailey AM (2017) Natural products from filamentous fungi and production by heterologous expression. Appl Microbiol Biotechnol 101:493–500. https://doi.org/10.1007/s00253-016-8034-2

    Article  CAS  PubMed  Google Scholar 

  7. Alhawatema MS, Gebril S, Cook D, Creamer R (2017) RNAi-mediated down-regulation of a melanin polyketide synthase (pks1) gene in the fungus Slafractonia leguminicola. World J Microbiol Biotechnol 33:179. https://doi.org/10.1007/s11274-017-2346-y

    Article  CAS  PubMed  Google Scholar 

  8. Altschul S, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410. https://doi.org/10.1016/S0022-2836(05)80360-2

    Article  CAS  Google Scholar 

  9. Ames BD, Nguyen C, Bruegger J, Smith P, Xu W, Ma S, Wong E, Wong S, Xie X, Li JWH, Vederas JC, Tang Y, Tsai SC (2012) Crystal structure and biochemical studies of the trans-acting polyketide enoyl reductase LovC from lovastatin biosynthesis. Proc Natl Acad Sci USA 109:11144–11149. https://doi.org/10.1073/pnas.1113029109

    Article  PubMed  Google Scholar 

  10. Araújo AA, de Melo MG, Rabelo TK, Nunes PS, Santos SL, Serafini MR, Santos MR, Quintans-Júnior LJ, Gelain DP (2015) Review of the biological properties and toxicity of usnic acid. Nat Prod Res 29:2167–2180. https://doi.org/10.1080/14786419.2015.1007455

    Article  CAS  PubMed  Google Scholar 

  11. Armaleo D, Sun X, Culberson C (2011) Insights from the first putative biosynthetic gene cluster for a lichen depside and depsidone. Mycologia 103:741–754. https://doi.org/10.3852/10-335

    Article  CAS  PubMed  Google Scholar 

  12. Bailey AM, Cox RJ, Harley K, Lazarus CM, Simpson TJ, Skellam E (2007) Characterization of 3-methylorcinaldehyde synthase (MOS) in Acremonium strictum: first observation of a reductive release mechanism during polyketide biosynthesis. Chem Commun 39:4053–4055. https://doi.org/10.1039/b708614h

    Article  CAS  Google Scholar 

  13. Barton DHR, Deflorin AM, Edwards OE (1956) The synthesis of usnic acid. J Chem Soc 1956:530–534. https://doi.org/10.1039/jr9560000530

    Article  Google Scholar 

  14. Bates ST, Cropsey GWG, Caporaso JG, Knight R, Fierer N (2011) Bacterial communities associated with the lichen symbiosis. Appl Environ Microbiol 77:1309–1314. https://doi.org/10.1128/AEM.02257-10

    Article  CAS  PubMed  Google Scholar 

  15. Bertrand RL, Abdel-Hameed M, Sorensen JL (2018) Lichen biosynthetic gene clusters part I: genome sequencing reveals a rich biosynthetic potential. J Nat Prod. https://doi.org/10.1021/acs.jnatprod.7b00769 (Epub ahead of print)

    Article  PubMed  Google Scholar 

  16. Bertrand RL, Abdel-Hameed M, Sorensen JL (2018) Lichen biosynthetic gene clusters part II: homology mapping suggests a functional diversity. J Nat Prod. https://doi.org/10.1021/acs.jnatprod.7b00770 (Epub ahead of print)

    Article  PubMed  Google Scholar 

  17. Bingle LE, Simpson TJ, Lazarus CM (1999) Ketosynthase domain probes identify two subclasses of fungal polyketide synthase genes. Fungal Genet Biol 26:209–223. https://doi.org/10.1006/fgbi.1999.1115

    Article  CAS  PubMed  Google Scholar 

  18. Blackwell M (2011) The fungi: 1,2,3,…5.1 million species? Am J Bot 98:426–438. https://doi.org/10.3732/ajb.1000298

    Article  Google Scholar 

  19. Blin K, Medema MH, Kazempour D, Fischbach MA, Breitling R, Takano E, Weber T (2013) AntiSMASH 2.0—a versatile platform for genome mining of secondary metabolite producers. Nucl Acids Res 41:W204–W212. https://doi.org/10.1093/nar/gkt449

    Article  PubMed  Google Scholar 

  20. Blin K, Wolf T, Chevrette MG, Lu X, Schwalen CJ, Kautsar SA, Suarez-Duran HG, de Los Santos ELC, Kim HU, Nave M, Dickschat JS, Mitchell DA, Shelest E, Breitling R, Takano E, Lee SY, Weber T, Medema MH (2017) AntiSMASH 4.0—improvements in chemistry prediction and gene cluster boundary identification. Nucl Acids Res 45:W36–W41. https://doi.org/10.1093/nar/gkx319

    Article  CAS  PubMed  Google Scholar 

  21. Bode HB, Bethe B, Höfs R, Zeeck A (2002) Big effects from small changes: possible ways to explore nature’s chemical diversity. ChemBioChem 3:619–627. https://doi.org/10.1002/1439-7633(20020703)3:7%3c619:AID-CBIC619%3e3.0.CO;2-9

    Article  CAS  PubMed  Google Scholar 

  22. Brunauer G, Hager A, Grube M, Türk R, Stocker-Wörgötter E (2007) Alterations in secondary metabolism of aposymbiotically grown mycobionts of Xanthoria elegans and cultured resynthesis stages. Plant Physiol Biochem 45:146–151. https://doi.org/10.1016/j.plaphy.2007.01.004

    Article  CAS  PubMed  Google Scholar 

  23. Brunauer G, Muggia L, Stocker-Wörgötter E, Grube M (2009) A transcribed polyketide synthase gene from Xanthoria elegans. Mycol Res 113:82–92. https://doi.org/10.1016/j.mycres.2008.08.007

    Article  CAS  PubMed  Google Scholar 

  24. Cacho RA, Tang Y, Chooi Y (2015) Next-generation sequencing approach for connecting secondary metabolites to biosynthetic gene clusters in fungi. Front Microbiol 5:774. https://doi.org/10.3389/fmicb.2014.00774

    Article  PubMed  PubMed Central  Google Scholar 

  25. Calcott MJ, Ackerley DF, Knight A, Keyzers RA, Owen JG (2018) Secondary metabolism in the lichen symbiosis. Chem Soc Rev 47:1730–1760. https://doi.org/10.1039/C7CS00431A

    Article  CAS  PubMed  Google Scholar 

  26. Campbell CD, Vederas JC (2010) Biosynthesis of lovastatin and related metabolites formed by fungal iterative PKS enzymes. Biopolymers 93:755–763. https://doi.org/10.1002/bip.21428

    Article  CAS  PubMed  Google Scholar 

  27. Chan YA, Podevels AM, Kevany BM, Thomas MG (2009) Biosynthesis of polyketide synthase extender units. Nat Prod Rep 26:90–114. https://doi.org/10.1039/B801658P

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chiang YM, Oakley BR, Keller NP, Wang CC (2010) Unraveling polyketide synthesis in members of the genus Aspergillus. Appl Microbiol Biotechnol 86:1719–1736. https://doi.org/10.1007/s00253-010-2525-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Chooi YH, Stalker DM, Davis MA, Fujii I, Elix JA, Louwhoff SHJJ, Lawrie AC (2008) Cloning and sequence characterization of a non-reducing polyketide synthase gene from the lichen Xanthoparmelia semiviridis. Mycol Res 112:147–161. https://doi.org/10.1016/j.mycres.2007.08.022

    Article  CAS  PubMed  Google Scholar 

  30. Cox RJ (2007) Polyketides, proteins and genes in fungi: programmed nano-machines begin to reveal their secrets. Org Biomol Chem 5:2010–2026. https://doi.org/10.1039/b704420h

    Article  CAS  PubMed  Google Scholar 

  31. Crawford JM, Dancy BCR, Hill EA, Udwary DW, Townsend CA (2006) Identification of a starter unit acyl-carrier protein transacylase domain in an iterative type I polyketide synthase. Proc Natl Acad Sci USA 103:16728–16733. https://doi.org/10.1073/pnas.0604112103

    Article  CAS  PubMed  Google Scholar 

  32. Crawford JM, Korman TP, Labonte JW, Vagstad AL, Hill EA, Kamari-Bidkorpeh O, Tsai SC, Townsend CA (2009) Structural basis for biosynthetic programming of fungal aromatic polyketide cyclization. Nature 461:1139–1143. https://doi.org/10.1038/nature08475

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Culberson CF, Armaleo D (1992) Induction of a complete secondary-product pathway in a cultured lichen fungus. Exp Mycol 16:52–63. https://doi.org/10.1016/0147-5975(92)90041-O

    Article  CAS  Google Scholar 

  34. Dal Grande F, Meiser A, Greshake Tzovaras B, Otte J, Ebersberger I, Schmitt I (2018) The draft genome sequence of the lichen-forming fungus Lasallia hispanica (Frey) Sancho & A. Crespo. Lichenologist 50:329–340. https://doi.org/10.1017/S002428291800021X

    Article  Google Scholar 

  35. Deduke C, Timsina B, Piercey-Normore MD (2012) Effect of environmental change on secondary metabolite production in lichen-forming fungi. In: Young SS, Silvern SE (eds) International perspectives on global environmental change. InTech, Croatia, pp 197–230. https://doi.org/10.5772/26954

    Chapter  Google Scholar 

  36. Doroghazi JR, Albright JC, Goering AW, Ju KS, Haines RR, Tchalukov KA, Labeda DP, Kelleher NL, Metcalf WW (2014) A roadmap for natural product discovery based on large-scale genomics and metabolomics. Nat Chem Biol 10:963–968. https://doi.org/10.1038/nchembio.1659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Du L, Lou L (2010) PKS and NRPS release mechanisms. Roy Soc Chem 27:255–278. https://doi.org/10.1039/B912037H

    Article  CAS  Google Scholar 

  38. Elshobary ME, Osman ME, Abo-Shady AM, Komatsu E, Perreault H, Sorensen J, Piercey-Normore MD (2016) Algal carbohydrates affect polyketide synthesis of the lichen-forming fungus Cladonia rangiferina. Mycologia 108:646–656. https://doi.org/10.3852/15-263

    Article  CAS  PubMed  Google Scholar 

  39. Fujii I, Mori Y, Watanabe A, Kubo Y, Tsuji G, Ebizuka Y (2000) Enzymatic synthesis of 1,3,6,8-tetrahydroxynaphthalene solely from malonyl coenzyme A by a fungal iterative type I polyketide synthase PKS1. Biochemistry 39:9953–9958. https://doi.org/10.1021/bi000644j

    Article  CAS  Google Scholar 

  40. 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 8:189–197. https://doi.org/10.1016/S1074-5521(00)90068-1

    Article  CAS  PubMed  Google Scholar 

  41. Fuller KK, Chen S, Loros JJ, Dunlap JC (2015) Development of the CRISPR/Cas9 system for targeted gene disruption in Aspergillus fumigatus. Eukaryot Cell 14:1073–1080. https://doi.org/10.1128/EC.00107-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Gagunashvili AN, Davídsson SP, Jónsson ZO, Andrésson ÓS (2009) Cloning and heterologous transcription of a polyketide synthase gene from the lichen Solorina crocea. Mycol Res 113:354–363. https://doi.org/10.1016/j.mycres.2008.11.011

    Article  CAS  PubMed  Google Scholar 

  43. Gomez-Escribano JP, Bibb MJ (2014) Heterologous expression of natural product biosynthetic gene clusters in Streptomyces coelicolor: from genome mining to manipulation of biosynthetic pathways. J Ind Microbiol Biotechnol 41:425–431. https://doi.org/10.1007/s10295-013-1348-5

    Article  CAS  PubMed  Google Scholar 

  44. Goodwin S, McPherson JD, McCombie WR (2016) Coming of age: ten years of next-generation sequencing technologies. Net Rev Genet 17:333–351. https://doi.org/10.1038/nrg.2016.49

    Article  CAS  Google Scholar 

  45. Grube M, Berg G, Andrésson ÓS, Vilhelmsson O, Dyer PS, Miao VPW (2014) Lichen genomics: prospects and progress. In: Martin F (ed) The ecological genomics of fungi. Wiley, New York, pp 191–212. https://doi.org/10.1002/9781118735893

    Chapter  Google Scholar 

  46. Grube M, Cardinale M, de Castro JV, Jr Müller H, Berg G (2009) Species-specific structural and functional diversity of bacterial communities in lichen symbioses. ISME J 3:1105–1115. https://doi.org/10.1038/ismej.2009.63

    Article  PubMed  Google Scholar 

  47. Gu L, Eisman EB, Dutta S, Franzmann TM, Walter S, Gerwick WH, Skiniotis G, Sherman DH (2011) Tandem acyl carrier proteins in the curacin biosynthesis pathway promotes consecutive multienzyme reactions with a synergistic effect. Angew Chem Int Ed 50:2795–2798. https://doi.org/10.1002/anie.201005280

    Article  CAS  Google Scholar 

  48. Gu L, Geders TW, Wang B, Gerwick WH, Håkansson K, Smith JL, Sherman DH (2007) GNAT-like strategy for polyketide chain initiation. Science 318:970–974. https://doi.org/10.1126/science.1148790

    Article  CAS  PubMed  Google Scholar 

  49. Guo C, Wang CC (2014) Recent advances in genome mining of secondary metabolites in Aspergillus terreus. Front Microbiol 5:717. https://doi.org/10.3389/fmicb.2014.00717

    Article  PubMed  PubMed Central  Google Scholar 

  50. Guo J, Wang Y, Li B, Huang S, Chen Y, Guo X, Xiao D (2017) Development of a one-step gene knock-out and knock-in method for metabolic engineering of Aureobasidium pullulans. J Biotechnol 251:145–150. https://doi.org/10.1016/j.jbiotec.2017.04.029

    Article  CAS  PubMed  Google Scholar 

  51. Hametner C, Stocker-Wörgötter E (2015) Type I NR-PKS gene characterization of the cultured lichen mycobiont Xanthoparmelia substrigosa (Ascomycota). In: Upreti DK, Shukla V, Bajpai R (eds) Recent advances in lichenology: modern methods and approaches in Lichen systematics and culture techniques, vol 2. Springer, India, pp 95–110. https://doi.org/10.1007/978-81-322-2235-4_5

    Chapter  Google Scholar 

  52. Hayashi S, Satoh Y, Ujihara T, Takata Y, Dairi T (2016) Enhanced production of polyunsaturated fatty acids by enzyme engineering of tandem acyl carrier proteins. Sci Rep 6:35441. https://doi.org/10.1038/srep35441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Helfrich EJN, Piel J (2016) Biosynthesis of polyketides by trans-AT polyketide synthases. Nat Prod Rep 33:231–316. https://doi.org/10.1039/C5NP00125K

    Article  CAS  PubMed  Google Scholar 

  54. Hosaka T, Ohnishi-Kaneyama M, Muramatsu H, Murakami K, Tsurumi Y, Kodani S, Yoshida M, Fujie A, Ochi K (2009) Antibacterial discovery in actinomycetes strains with mutations in RNA polymerase or ribosomal protein S12. Nat Biotechnol 27:462–464. https://doi.org/10.1038/nbt.1538

    Article  CAS  PubMed  Google Scholar 

  55. Huang G, Zhang L, Birch RG (2001) A multifunctional polyketide-peptide synthetase essential for albicidin biosynthesis in Xanthomonas albilineans. Microbiology 147:631–642. https://doi.org/10.1099/00221287-147-3-631

    Article  CAS  PubMed  Google Scholar 

  56. Huneck S, Yoshimura Y (1996) Identification of lichen substances. Springer, New York. https://doi.org/10.1007/978-3-642-85243-5

    Book  Google Scholar 

  57. Hunter S, Apweiler R, Attwood TK, Bairoch A, Bateman A, Binns D, Bork P, Das U, Daugherty L, Duquenne L, Finn RD, Gough J, Haft D, Hulo N, Kahn D, Kelly E, Laugraud A, Letunic I, Lonsdale D, Lopez R, Madera M, Maslen J, McAnulla C, McDowall J, Mistry J, Mitchell A, Mulder N, Natale D, Orengo C, Quinn AF, Selengut JD, Sigrist CJA, Thimma M, Thomas PD, Valentin F, Wilson D, Wu CH, Yeats C (2009) InterPro: the integrative protein signature database. Nucl Acids Res 37:D211–D215. https://doi.org/10.1093/nar/gkn785

    Article  CAS  PubMed  Google Scholar 

  58. Jeong MH, Kim JA, Yu NH, Jung JS, Hong SG, Cheong YH, Hur JS (2015) Isolation and characterization of a non-reducing polyketide synthase gene in Cladonia macilenta. Mycoscience 56:49–57. https://doi.org/10.1016/j.myc.2014.03.001

    Article  CAS  Google Scholar 

  59. Jiang H, Zirkle R, Metz JG, Braun L, Richter L, van Lanen SG, Shen B (2008) The role of tandem-acyl carrier protein domains in polyunsaturated fatty acid biosynthesis. J Am Chem Soc 130:6336–6337. https://doi.org/10.1021/ja801911t

    Article  CAS  PubMed  Google Scholar 

  60. Kaasalainen U, Fewer DP, Jokela J, Wahlsten M, Sivonen K, Rikkinen J (2012) Cyanobacteria produce a high variety of hepatotoxic peptides in lichen symbiosis. Proc Natl Acad Sci USA 109:5886–5891. https://doi.org/10.1073/pnas.1200279109

    Article  PubMed  Google Scholar 

  61. Kampa A, Gagunashvili AN, Gulder TAM, Morinaka BI, Daolio C, Godejohann M, Miao VPW, Piel J, Andrésson ÓS (2013) Metagenomic natural product discovery in lichen provides evidence for a family of biosynthetic pathways in diverse symbioses. Proc Natl Acad Sci USA 110:E3129–E3137. https://doi.org/10.1073/pnas.1305867110

    Article  PubMed  Google Scholar 

  62. Katz L, Baltz RH (2016) Natural product discovery: past, present, and future. J Ind Microbiol Biotechnol 43:155–176. https://doi.org/10.1007/s10295-015-1723-5

    Article  CAS  PubMed  Google Scholar 

  63. Kim JA, Hong SG, Cheong YH, Koh YJ, Hur JS (2012) A new reducing polyketide synthase gene from the lichen-forming fungus Cladonia metacorallifera. Mycologia 104:362–370. https://doi.org/10.3852/11-001

    Article  CAS  PubMed  Google Scholar 

  64. Lim YP, Go MK, Yew WS (2016) Exploiting the biosynthetic potential of type III polyketide synthases. Molecules 21:806. https://doi.org/10.3390/molecules21060806

    Article  CAS  Google Scholar 

  65. Lopes TI, Coelho RG, Yoshida NC, Honda NK (2008) Radical scavenging activity of orsellinates. Chem Pharm Bull Tokyo 56:1151–1554. https://doi.org/10.1248/cpb.56.1551

    Article  Google Scholar 

  66. Lucia M, Martin G (2010) Type III polyketide synthases in lichen mycobionts. Fungal Biol 114:379–385. https://doi.org/10.1016/j.funbio.2010.03.001

    Article  CAS  PubMed  Google Scholar 

  67. Luo Y, Cobb RE, Zhao H (2014) Recent advances in natural product discovery. Curr Opin Biotechnol 30:230–237. https://doi.org/10.1016/j.copbio.2014.09.002

    Article  CAS  PubMed  Google Scholar 

  68. Lutzoni F, Miadlikowska J (2009) Lichens. Curr Biol 19:R502–R503. https://doi.org/10.1016/j.cub.2009.04.034

    Article  CAS  PubMed  Google Scholar 

  69. Miao V, Coëffet-LeGal M-F, Brown D, Sinnemann S, Donaldson G, Davies J (2001) Genetic approaches to harvesting lichen products. Trends Biotechnol 19:349–355. https://doi.org/10.1016/S0167-7799(01)01700-0

    Article  CAS  PubMed  Google Scholar 

  70. Miao V, Davies J (1997) Molecular diversity of polyketide biosynthesis genes in lichens. In: Baltz RH, Hegeman GD, Skatrud PL (eds) Developments in industrial microbiology. Society for Industrial Microbiology, Fairfax, pp 57–60

    Google Scholar 

  71. Minto RE, Townsend CA (1997) Enzymology and molecular biology of aflatoxin biosynthesis. Chem Rev 97:2537–2556. https://doi.org/10.1021/cr960032y

    Article  CAS  PubMed  Google Scholar 

  72. Nash TH III (2008) Lichen biology, 2nd edn. Cambridge University Press, Cambridge. https://doi.org/10.1017/CBO9780511790478

    Book  Google Scholar 

  73. Nguyen KH, Chollet-Krugler M, Gouault N, Tomasi S (2013) UV-protectant metabolites from lichens and their symbiotic partners. Nat Prod Rep 30:1490–1508. https://doi.org/10.1039/c3np70064j

    Article  CAS  PubMed  Google Scholar 

  74. Nguyen T, Ishida K, Jenke-Kodama H, Dittmann E, Gurgui C, Hochmuth T, Taudien S, Platzer M, Hertweck C, Piel J (2008) Exploiting the mosaic structure of trans-acyltransferase polyketide synthases for natural product discovery and pathway dissection. Nat Biotechnol 26:225–233. https://doi.org/10.1038/nbt1379

    Article  CAS  PubMed  Google Scholar 

  75. Nicholson TP, Rudd BAM, Dawson M, Lazarus CM, Simpson TJ, Cox RJ (2001) Design and utility of oligonucleotide gene probes for fungal polyketide synthases. Chem Biol 8:157–178. https://doi.org/10.1016/S1074-5521(00)90064-4

    Article  CAS  PubMed  Google Scholar 

  76. Nielsen JC, Grijseels S, Prigent S, Ji B, Dainat J, Nielsen KF, Frisvad JC, Workman M, Nielsen J (2017) Global analysis of biosynthetic gene clusters reveals vast potential of secondary metabolite production in Penicillium species. Nat Microbiol 2:17044. https://doi.org/10.1038/nmicrobiol.2017.44

    Article  CAS  PubMed  Google Scholar 

  77. Onaka H, Mori Y, Igarashi Y, Furumai T (2011) Mycolic acid-containing bacteria induce natural-product biosynthesis in Streptomyces species. Appl Environ Microbiol 77:400–406. https://doi.org/10.1128/AEM.01337-10

    Article  CAS  PubMed  Google Scholar 

  78. Park SY, Jeong MH, Wang HY, Kim JA, Yu NH, Kim S, Cheong YH, Kang S, Lee YH, Hur JS (2013) Agrobacterium tumefaciens-mediated transformation of the lichen fungus, Umbilicaria muehlenbergii. PLoS One 8:e83896. https://doi.org/10.1371/journal.pone.0083896

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Park SY, Choi J, Kim JA, Yu NH, Kim S, Kondratyuk SY, Lee YH, Hur JS (2013) Draft genome sequence of lichen-forming fungus Caloplaca flavorubescens strain KoLRI002931. Genome Announc 1:e00678-13. https://doi.org/10.1128/genomeA.00678-13

    Article  PubMed  PubMed Central  Google Scholar 

  80. Park SY, Choi J, Kim JA, Jeong MH, Kim S, Lee YH, Hur JS (2013) Draft genome sequence of Cladonia macilenta KoLRI003786, a lichen-forming fungus producing biruloquinone. Genome Announc 1:e00695-13. https://doi.org/10.1128/genomeA.00695-13

    Article  PubMed  PubMed Central  Google Scholar 

  81. Park SY, Choi J, Lee GW, Kim JA, Oh SO, Jeong MH, Yu NH, Kim S, Lee YH, Hur JS (2014) Draft genome sequence of lichen-forming fungus Cladonia metacorallifera strain KoLRI002260 Genome. Announc 2:e01065-13. https://doi.org/10.1128/genomeA.01065-13

    Article  Google Scholar 

  82. Park SY, Choi J, Lee GW, Park CH, Kim JA, Oh SO, Lee YH, Hur JS (2014) Draft genome sequence of Endocarpon pusillum strain KoLRILF000583. Genome Announc 2:e00452-14. https://doi.org/10.1128/genomeA.00452-14

    Article  PubMed  PubMed Central  Google Scholar 

  83. Park SY, Choi J, Lee GW, Jeong MH, Kim JA, Oh SO, Lee YH, Hur JS (2014) Draft genome sequence of Umbilicaria muehlenbergii KoLRILF000956, a lichen-forming fungus amenable to genetic manipulation. Genome Announc 2(2):e00357-14. https://doi.org/10.1128/genomeA.00357-14

    Article  PubMed  PubMed Central  Google Scholar 

  84. Polborn K, Steglich W, Connolly JD, Huneck S (1995) Structure of the macrocyclic bis-lactone lepranthin from the lichen Arthonia impolita; an X-ray analysis. Z Naturforsch B Chem Sci 50:1111–1114. https://doi.org/10.1515/znb-1995-0723

    Article  CAS  Google Scholar 

  85. Puel O, Galtier P, Oswald IP (2010) Biosynthesis and toxicological effects of patulin. Toxins 2:613–631. https://doi.org/10.3390/toxins2040613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Rahman AS, Hothersall J, Crosby J, Simpson TJ, Thomas CM (2005) Tandemly duplicated acyl carrier proteins, which increase polyketide antibiotic production, can apparently function either in parallel or in series. J Biol Chem 280:6399–6408. https://doi.org/10.1074/jbc.M409814200

    Article  CAS  PubMed  Google Scholar 

  87. Roze LV, Hong SY, Linz JE (2013) Aflatoxin biosynthesis: current frontiers. Annu Rev Food Sci Technol 4:293–311. https://doi.org/10.1146/annurev-food-083012-123702

    Article  CAS  PubMed  Google Scholar 

  88. Schmitt I, Kautz S, Lumbsch HT (2008) 6-MSAS-like polyketide synthase genes occur in lichenized ascomycetes. Mycol Res 112:289–296. https://doi.org/10.1016/j.mycres.2007.08.023

    Article  CAS  PubMed  Google Scholar 

  89. Schorn MA, Alanjary MM, Aquinaldo K, Korobeynikov A, Podell S, Patin N, Linecum T, Jensen PR, Ziemert N, Moore BS (2016) Sequencing rare marine actinomycete genomes reveals high density of unique natural product biosynthetic gene clusters. Microbiology 162:2075–2086. https://doi.org/10.1099/mic.0.000386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Sharma R, Tiku AB, Giri A (2017) Pharmacological properties of emodin—anthraquinone derivatives. J Nat Prod Resour 3:97–101

    Google Scholar 

  91. Shimizu Y, Ogata H, Goto S (2017) Type III polyketide synthases: functional classification and phylogenomics. ChemBioChem 18:50–65. https://doi.org/10.1002/cbic.201600522

    Article  CAS  PubMed  Google Scholar 

  92. Shrestha G, St. Clair LL (2013) Lichens: a promising source of antibiotic and anticancer drugs. Phytochem Rev 12:229–244. https://doi.org/10.1007/s11101-013-9283-7

    Article  CAS  Google Scholar 

  93. Simpson TJ, Cox RJ (2012) Polyketides in fungi. In: Civjan N (ed) Natural products in chemical biology. Wiley, New Jersey, pp 141–161. https://doi.org/10.1002/9781118391815.ch6

    Chapter  Google Scholar 

  94. Sinnemann SJ, Andrésson OS, Brown DW, Miao VP (2000) Cloning and heterologous expression of Solorina crocea pyrG. Curr Genet 37:333–338. https://doi.org/10.1007/s002940050536

    Article  CAS  PubMed  Google Scholar 

  95. Spribille T, Tuovinen V, Resl P, Vanderpool D, Wolinski H, Aime MC, Schneider K, Stabentheiner E, Toome-Heller M, Thor G, Mayrhofer H, Johannesson H, McCutcheon JP (2016) Basidiomycete yeasts in the cortex of ascomycete macrolichens. Science 353:488–492. https://doi.org/10.1126/science.aaf8287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Staunton J, Weissman KJ (2001) Polyketide biosynthesis: a millennium review. Nat Prod Rep 18:380–416. https://doi.org/10.1039/a909079g

    Article  CAS  PubMed  Google Scholar 

  97. Studzinska-Stroka E, Galanty A, Bylka W (2017) Atranorin—an interesting lichen secondary metabolite. Mini Rev Med Chem 17:1633–1645. https://doi.org/10.2174/1389557517666170425105727

    Article  CAS  Google Scholar 

  98. Stocker-Wörgötter AE, Elix JA, Grube M (2004) Secondary chemistry of lichen-forming fungi: chemosyndromic variation and DNA-analyses of cultures and chemotypes in the Ramalina farinacea complex. Bryologist 107:152–162. https://doi.org/10.1639/0007-2745(2004)107%5b0152:SCOLFC%5d2.0.CO;2

    Article  Google Scholar 

  99. Stocker-Wörgötter E, Hager A (2008) Appendix: culture methods for lichens and lichen symbionts. In: Nash TH III (ed) Lichen Biology, 2nd edn. Cambridge University Press, Cambridge, pp 353–363. https://doi.org/10.1017/CBO9780511790478.019

    Chapter  Google Scholar 

  100. Suroto DA, Kitani S, Miyamoto KT, Sakihama Y, Arai M, Ikeda H, Nihira T (2017) Activation of cryptic phthoxazolin A production in Streptomyces avermitilis by the disruption of autoregulator-receptor homologue AvaR3. J Biosci Bioeng 124:611–617. https://doi.org/10.1016/j.jbiosc.2017.06.014

    Article  CAS  PubMed  Google Scholar 

  101. Taguchi H, Sankawa U, Shibata S (1969) Biosynthesis of usnic acid in lichens. VI. Biosynthesis of usnic acid in lichens: a general scheme of biosynthesis of usnic acid. Chem Pharm Bull 17:2054–2060. https://doi.org/10.1248/cpb.17.2054

    Article  CAS  PubMed  Google Scholar 

  102. Tanaka Y, Hosaka T, Ochi K (2010) Rare earth elements activate the secondary metabolite-biosynthetic gene clusters in Streptomyces coelicolor A3(2). J Antibiot 63:477–481. https://doi.org/10.1038/ja.2010.53

    Article  CAS  PubMed  Google Scholar 

  103. Timsina BA, Hausner G, Piercey-Normore MD (2014) Evolution of ketosynthase domains of polyketide synthase genes in the Cladonia chlorophaea species complex (Cladoniaceae). Fungal Biol 118:896–909. https://doi.org/10.1016/j.funbio.2014.08.001

    Article  CAS  PubMed  Google Scholar 

  104. Timsina BA, Sorensen JL, Weihrauch D, Piercey-Normore MD (2013) Effect of aposymbiotic conditions on colony growth and secondary metabolite production in the lichen-forming fungus, Ramalina dilacerata. Fungal Biol 117:731–743. https://doi.org/10.1016/j.funbio.2013.09.003

    Article  CAS  PubMed  Google Scholar 

  105. Timsina BA, Stocker-Wörgötter E, Piercey-Normore MD (2012) Monophyly of some North American species of Ramalina and inferred polyketide synthase gene function. Botany 90:1295–1307. https://doi.org/10.1139/b2012-097

    Article  CAS  Google Scholar 

  106. Valarmathi R, Hariharan GN, Venkataraman G, Parida A (2009) Characterization of a non-reducing polyketide synthase gene from lichen Dirinaria applanata. Phytochemistry 70:721–729. https://doi.org/10.1016/j.phytochem.2009.04.007

    Article  CAS  PubMed  Google Scholar 

  107. Vetting MW, Carvalho LPS, Yu M, Hegde SS, Magnet S, Roderick SL, Blanchard JS (2005) Structure and function of the GNAT superfamily of acetyltransferases. Arch Biochem Biophys 433:212–226. https://doi.org/10.1016/j.abb.2004.09.003

    Article  CAS  PubMed  Google Scholar 

  108. Wang Y, Kim JA, Cheong YH, Joshi Y, Koh YJ, Hur JS (2011) Isolation and characterization of a reducing polyketide synthase gene from the lichen-forming fungus Usnea longissima. J Microbiol 49:473–480. https://doi.org/10.1007/s12275-011-0362-4

    Article  CAS  PubMed  Google Scholar 

  109. Wang Y, Kim JA, Cheong YH, Koh YJ, Hur JS (2012) Isolation and characterization of a non-reducing polyketide synthase gene from the lichen-forming fungus Usnea longissima. Mycol Prog 11:75–83. https://doi.org/10.1007/s11557-010-0730-1

    Article  CAS  Google Scholar 

  110. Wang Y, Liu B, Zhang X, Zhou Q, Zhang T, Li H, Yu Y, Zhang X, Hao X, Wang M, Wang L, Wei J (2014) Genome characteristics reveal the impact of lichenization on lichen-forming fungus Endocarpon pusillum Hedwig (Verrucariales, Ascomycota). BMC Genomics 15:34. https://doi.org/10.1186/1471-2164-15-34

    Article  PubMed  PubMed Central  Google Scholar 

  111. Wang Y, Geng C, Yuan X, Hua M, Tian F, Changtian Li (2018) Identification of a putative polyketide synthase gene involved in usnic acid biosynthesis in the lichen Nephromopsis pallescens. PLoS One 13:e0199110. https://doi.org/10.1371/journal.pone.0199110

    Article  PubMed  PubMed Central  Google Scholar 

  112. Wang Y, Yuan X, Chen L, Wang X, Li C (2018) Draft genome sequence of the lichen-forming fungus Ramalina intermedia strain YAF0013. Genome Announc 6:e00478-18. https://doi.org/10.1128/genomeA.00478-18

    Article  PubMed  PubMed Central  Google Scholar 

  113. Wang Y, Wang J, Cheong YH, Hur J-S (2014) Three new non-reducing polyketide synthase genes from the lichen-forming fungus Usnea Longissima. Mycobiology 42:34–40. https://doi.org/10.5941/MYCO.2014.42.1.34

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Wang Y, Zhao N, Yuan X, Hua M, Jae-Seoun H, Yang Y, Wang J (2016) Heterologous transcription of a polyketide synthase gene from the lichen forming fungi Usnea longissima. Res J Biotechnol 10:16–21

    Google Scholar 

  115. Wang Y, Zhen X, Hur JS, Wang J (2014) Isolation and characterization of a polyketide synthase gene cluster from Usnea Longissima. Acta Microbiologica Sinica 54:770–777

    CAS  PubMed  Google Scholar 

  116. Weissman KJ (2015) Uncovering the structures of modular polyketide synthases. Nat Prod Rep 32:436–453. https://doi.org/10.1039/C4NP00098F

    Article  CAS  PubMed  Google Scholar 

  117. Xu X, Liu L, Zhang F, Wang W, Li J, Guo L, Che Y, Liu G (2014) Identification of the first diphenyl ether gene cluster for pestheic acid biosynthesis in plant endophyte Pestalotiopsis fici. ChemBioChem 15:284–292. https://doi.org/10.1002/cbic.201300626

    Article  CAS  PubMed  Google Scholar 

  118. Ye S, Molloy B, Braña AF, Zabala D, Olano C, Cortés J, Moris F, Salas JA, Méndez C (2017) Identification by genome mining of a type I polyketide gene cluster from Streptomyces argillaceus involved in the biosynthesis of pyridine and piperidine alkaloids argimycins P. Front Microbiol 8:194. https://doi.org/10.3389/fmicb.2017.00194

    Article  PubMed  PubMed Central  Google Scholar 

  119. Yeku O, Frohman MA (2011) Rapid amplification of cDNA ends (RACE). Methods Mol Biol 703:107–122. https://doi.org/10.1007/978-1-59745-248-9_8

    Article  CAS  PubMed  Google Scholar 

  120. Yu JH, Leonard TJ (1995) Sterigmatocystin biosynthesis in Aspergillus nidulans requires a novel type I polyketide synthase. J Bacteriol 177:4792–4800. https://doi.org/10.1128/jb.177.16.4792-4800.1995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Yu NH, Kim JA, Jeong MH, Cheong YH, Jung JS, Hur JS (2013) Characterization of two novel non-reducing polyketide synthase genes from the lichen-forming fungus Hypogymnia physodes. Mycol Prog 12:519–524. https://doi.org/10.1007/s11557-012-0858-2

    Article  Google Scholar 

  122. Zabala D, Braña AF, Flórez AB, Salas JA, Méndez C (2013) Engineering precursor metabolite pools for increasing production of antitumor mithramycins in Streptomyces argillaceus. Metab Eng 20:187–197. https://doi.org/10.1016/j.ymben.2013.10.002

    Article  CAS  PubMed  Google Scholar 

  123. Zaehle C, Gressler M, Shelest E, Geib E, Hertweck C, Brock M (2014) Terrein biosynthesis in Aspergillus terreus and its impact on phytotoxicity. Chem Biol 21:719–731. https://doi.org/10.1016/j.chembiol.2014.03.010

    Article  CAS  PubMed  Google Scholar 

  124. Zambare VP, Christopher LP (2012) Biopharmaceutical potential of lichens. Pharm Biol 50:778–798. https://doi.org/10.3109/13880209.2011.633089

    Article  PubMed  Google Scholar 

  125. Zhang MM, Wong FT, Wang Y, Luo S, Lim YH, Heng E, Yeo WL, Cobb RE, Enghiad B, Ang EL, Zhao H (2017) CRISPR-Cas9 strategy for activation of silent Streptomyces biosynthetic gene clusters. Nat Chem Biol 13:607. https://doi.org/10.1038/nchembio.2341

    Article  CAS  Google Scholar 

  126. Ziemert N, Alanjary M, Weber T (2016) The evolution of genome mining in microbes—a review. Nat Prod Rep 33:988–1005. https://doi.org/10.1039/C6NP00025H

    Article  CAS  PubMed  Google Scholar 

  127. Ziemert N, Jensen PR (2012) Phylogenetic approaches to natural product structure prediction. Methods Enzymol 517:161–182. https://doi.org/10.1016/B978-0-12-404634-4.00008-5

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors acknowledge a National Sciences and Engineering Research Council of Canada (NSERC) Discovery Grant awarded to JLS, and an NSERC post-graduate scholarship awarded to RLB.

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Bertrand, R.L., Sorensen, J.L. A comprehensive catalogue of polyketide synthase gene clusters in lichenizing fungi. J Ind Microbiol Biotechnol 45, 1067–1081 (2018). https://doi.org/10.1007/s10295-018-2080-y

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