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.
Similar content being viewed by others
References
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)
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
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
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
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
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
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
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
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
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
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
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
Barton DHR, Deflorin AM, Edwards OE (1956) The synthesis of usnic acid. J Chem Soc 1956:530–534. https://doi.org/10.1039/jr9560000530
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
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)
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)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Du L, Lou L (2010) PKS and NRPS release mechanisms. Roy Soc Chem 27:255–278. https://doi.org/10.1039/B912037H
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Huneck S, Yoshimura Y (1996) Identification of lichen substances. Springer, New York. https://doi.org/10.1007/978-3-642-85243-5
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
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
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
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
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
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
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
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
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
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
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
Lutzoni F, Miadlikowska J (2009) Lichens. Curr Biol 19:R502–R503. https://doi.org/10.1016/j.cub.2009.04.034
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
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
Minto RE, Townsend CA (1997) Enzymology and molecular biology of aflatoxin biosynthesis. Chem Rev 97:2537–2556. https://doi.org/10.1021/cr960032y
Nash TH III (2008) Lichen biology, 2nd edn. Cambridge University Press, Cambridge. https://doi.org/10.1017/CBO9780511790478
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
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
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
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
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
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
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
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
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
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
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
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
Puel O, Galtier P, Oswald IP (2010) Biosynthesis and toxicological effects of patulin. Toxins 2:613–631. https://doi.org/10.3390/toxins2040613
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
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
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
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
Sharma R, Tiku AB, Giri A (2017) Pharmacological properties of emodin—anthraquinone derivatives. J Nat Prod Resour 3:97–101
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
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
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
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
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
Staunton J, Weissman KJ (2001) Polyketide biosynthesis: a millennium review. Nat Prod Rep 18:380–416. https://doi.org/10.1039/a909079g
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Weissman KJ (2015) Uncovering the structures of modular polyketide synthases. Nat Prod Rep 32:436–453. https://doi.org/10.1039/C4NP00098F
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
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
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
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
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
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
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
Zambare VP, Christopher LP (2012) Biopharmaceutical potential of lichens. Pharm Biol 50:778–798. https://doi.org/10.3109/13880209.2011.633089
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
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
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
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.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
There are no conflicts of interests to declare.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10295-018-2080-y