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Mycological Progress

, Volume 18, Issue 12, pp 1437–1447 | Cite as

Transcriptional heterologous expression of two type III PKS from the lichen Cladonia uncialis

  • Robert L. Bertrand
  • John L. SorensenEmail author
Original Article
  • 69 Downloads

Abstract

Type III polyketide synthases (PKS) are an under-explored group of enzymes that are responsible for producing a variety of bioactive molecules. In a previous study, we identified two type III PKS genes (t3pks1 and t3pks2) in the lichenizing fungus Cladonia uncialis. Here, we report efforts to functionally characterize these PKS using bioinformatics and heterologous expression. Phylogenetic analysis of t3pks1 indicated that the encoded PKS produces an alkylresorcinol. To estimate the size of the polyketide produced by T3PKS1, crystal structures of fungal type III PKS known to produce alkylresorcinols were examined. A strong correlation (R2 = 0.85) was observed between the active site cavity volume and the size of the largest alkylresorcinol produced by these PKS. Cavity volume measurements of modeled T3PKS1 suggested that this PKS can recruit long (C20) fatty acid-CoA primers to produce a polyketide of approximately 400 g/mol. To functionally characterize both lichen PKS, the t3pks1 and t3pks2 genes were transformed into NSAR1 Aspergillus oryzae. Transcriptional heterologous expression (including intron removal) of both genes was achieved. However, no new metabolites were observed within the host. This study is the first attempt to functionally characterize type III PKS from lichen fungi.

Graphical abstract

Keywords

Heterologous expression Protein modeling Resorcinol Fatty acids Phylogenetics Polyketides Lichen 

Notes

Acknowledgments

The authors thank Professor Ikuro Abe (Graduate School of Pharmacy, University of Tokyo) for providing the NSAR1 Aspergillus oryzae stain and the plasmids used throughout this work. The authors also thank Sabina Ozog and Vienna Peters (Department of Chemistry, University of Manitoba) for assistance in performing the metabolite screening.

Funding information

This work was supported by a Post-Graduate Scholarship awarded to RLB (460639-2014) and a Discovery Grant awarded to JLS, both from the Natural Sciences and Engineering Research Council of Canada.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11557_2019_1539_MOESM1_ESM.docx (617 kb)
ESM 1 (DOCX 616 kb).

References

  1. Abdel-Hameed M, Bertrand RL, Piercey-Normore MD, Sorensen JL (2016a) Putative identification of the usnic acid biosynthetic gene cluster by de novo whole-genome sequencing of a lichen-forming fungus. Fungal Biol 120:306–316.  https://doi.org/10.1016/j.funbio.2015.10.009 CrossRefPubMedGoogle Scholar
  2. Abdel-Hameed M, Bertrand RL, Piercey-Normore MD, Sorensen JL (2016b) 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 CrossRefPubMedGoogle Scholar
  3. 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 503:1228–1234.  https://doi.org/10.1016/j.bbrc.2018.07.029 CrossRefPubMedGoogle Scholar
  4. Abe I, Oguro S, Utsumi Y, Sano Y, Noguchi H (2005a) Engineered biosynthesis of plant polyketides: chain length control in an octaketide-producing plant type III polyketide synthase. J Am Chem Soc 127:12709–12716.  https://doi.org/10.1021/ja053945v CrossRefPubMedGoogle Scholar
  5. Abe I, Utsumi Y, Oguro S, Morita H, Sano Y, Noguchi H (2005b) A plant type III polyketide synthase that produces pentaketide chromone. J Am Chem Soc 127:1362–1363.  https://doi.org/10.1021/ja0431206 CrossRefPubMedGoogle Scholar
  6. Abe I, Watanabe T, Morita H, Kohno T, Noguchi H (2006) Engineered biosynthesis of plant polyketides: manipulation of chalcone synthase. Org Lett 8:499–502.  https://doi.org/10.1021/ol052912h CrossRefPubMedGoogle Scholar
  7. Abe I, Morita H, Oguro S, Noma H, Wanibuchi K, Kawahara N, Goda Y, Noguchi H, Kohno T (2007) Structure-based engineering of a plant type III polyketide synthase: formation of an unnatural nonaketide naphthropyrone. J Am Chem Soc 129:5976–5980.  https://doi.org/10.1021/ja070375l CrossRefPubMedGoogle Scholar
  8. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410.  https://doi.org/10.1006/jmbi.1990.9999 CrossRefGoogle Scholar
  9. Anyaogu DC, Mortensen UH (2015) Heterologous production of fungal secondary metabolites in Aspergilli. Front Microbiol 6:77.  https://doi.org/10.3389/fmicb.2015.00077 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 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 CrossRefPubMedGoogle Scholar
  11. Austin MB, Saito T, Bowman ME, Haydock S, Kato A, Moore BS, Kay RR, Noel JP (2006) Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid-type III polyketide synthase. Nat Chem Biol 2:494–502.  https://doi.org/10.1038/nchembio811 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Bailey AM, Alberti F, Kilaru S, Collins CM, de Mattos-Shipley K, Hartley AJ, Hayes P, Griffin A, Lazarus CM, Cox RJ, Willis CL, O’Dwyer K, Spence DW, Foster GD (2016) Identification and manipulation of the pleuromutilin gene cluster from Clitopilus passeckerianus for increased rapid antibiotic production. Sci Rep 6:25202.  https://doi.org/10.1038/srep25202 CrossRefPubMedPubMedCentralGoogle Scholar
  13. Baldauf SL (2003) Phylogeny for the faint of heart: a tutorial. Trends Genet 19:345–351.  https://doi.org/10.1016/S0168-9525(03)00112-4 CrossRefPubMedGoogle Scholar
  14. Bertrand RL, Sorensen JL (2018) A comprehensive catalogue of polyketide synthase gene clusters in lichenizing fungi. J Ind Microbiol Biotechnol 45:1067–1081.  https://doi.org/10.1007/s10295-018-2080-y CrossRefPubMedGoogle Scholar
  15. Bertrand RL, Sorensen JL (2019) Lost in translation: challenges with heterologous expression of lichen polyketide synthases. ChemistrySelect 4:1–12.  https://doi.org/10.1002/slct.201901762 CrossRefGoogle Scholar
  16. Bertrand RL, Abdel-Hameed M, Sorensen JL (2018a) Lichen biosynthetic gene clusters. Part I. Genome sequencing reveals a rich biosynthetic potential. J Nat Prod 81:723–731.  https://doi.org/10.1021/acs.jnatprod.7b00769 CrossRefPubMedGoogle Scholar
  17. Bertrand RL, Abdel-Hameed M, Sorensen JL (2018b) Lichen biosynthetic gene clusters part II: homology mapping suggests a functional diversity. J Nat Prod 81:732–748.  https://doi.org/10.1021/acs.jnatprod.7b00770 CrossRefPubMedGoogle Scholar
  18. Brobst SW, Townsend CA (1994) The potential role of fatty acid initiation in the biosynthesis of the fungal aromatic polyketide aflatoxin B1. Can J Chem 72:200–207.  https://doi.org/10.1139/v94-031 CrossRefGoogle Scholar
  19. Calchera A, Dal Grande F, Bode HB, Schmitt I (2019) Biosynthetic gene content of the ‘perfume lichens’ Evernia prunastri and Pseudevernia furfuracea. Molecules 24:203.  https://doi.org/10.3390/molecules24010203 CrossRefPubMedCentralGoogle Scholar
  20. 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 CrossRefPubMedGoogle Scholar
  21. Chemler JA, Buchholz TJ, Geders TW, Akey DL, Rath CM, Chlipala GE, Smith JL, Sherman DH (2012) Biochemical and structural characterization of germicidin synthase: analysis of a type III polyketide synthase that employs acyl-ACP as a starter unit donor. J Am Chem Soc 134:7359–7366.  https://doi.org/10.1021/ja2112228 CrossRefPubMedPubMedCentralGoogle Scholar
  22. Chester DO, Elix JA (1981) Condidymic acid, a new dibenzofuran from the lichen Cladonia squamosula. Aust J Chem 34:1501–1506.  https://doi.org/10.1071/CH9811501 CrossRefGoogle Scholar
  23. Chooi YH, Stalker DM, Davis MA, Fujii I, Elix JA, Louwhoff SH, 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 CrossRefPubMedGoogle Scholar
  24. Crawford SD (2015) Lichens used in traditional medicine. In: Ranković B (ed) Lichen secondary metabolites: bioactive properties and pharmaceutical potential. Springer, New York, pp 27–80.  https://doi.org/10.1007/978-3-319-13374-4_2 CrossRefGoogle Scholar
  25. Dal Grande F, Meiser A, Greshake Tzovaras B, Otte J, Ebersberger I, Schmitt I (2018) The draft genome of the lichen-forming fungus Lasallia hispanica (Frey) Sancho & A. Crespo Lichenologist 50:329–340.  https://doi.org/10.1017/S002428291800021X CrossRefGoogle Scholar
  26. Dorrestein PC, Van Lanen SG, Li W, Zhao C, Deng Z, Shen B, Kelleher NL (2006) The bifunctional glyceryl transferase/phosphatase OzmB belonging to the HAD superfamily that diverts 1,3-bisphosphoglycerate into polyketide biosynthesis. J Am Chem Soc 128:10386–10387.  https://doi.org/10.1021/ja0639362 CrossRefPubMedGoogle Scholar
  27. Edwards DJ, Marquez BL, Nogle LM, McPhail K, Goeger DE, Roberts MA, Gerwick WH (2004) Structure and biosynthesis of the jamaicamides, new mixed polyketide-peptide neurotoxins from the marine cyanobacterium Lyngbya majuscula. Chem Biol 11:817–833.  https://doi.org/10.1016/j.chembiol.2004.03.030 CrossRefPubMedGoogle Scholar
  28. Felsenstein J (1985) Confidence limits of phylogenies: an approach using the bootstrap. Evolution 39:783–791.  https://doi.org/10.1111/j.1558-5646.1985.tb00420.x CrossRefGoogle Scholar
  29. Ferrer JL, Jez JM, Bowman ME, Dixon RA, Noel JP (1999) Structure of chalcone synthase and the molecular basis of plant polyketide biosynthesis. Nat Struct Biol 6:775–784.  https://doi.org/10.1038/11553 CrossRefPubMedGoogle Scholar
  30. Fiser A (2010) Template-based protein structure modeling. Methods Mol Biol 673:73–94.  https://doi.org/10.1007/978-1-60761-842-3_6 CrossRefPubMedPubMedCentralGoogle Scholar
  31. Fujii R, Minami A, Tsukagoshi T, Sato N, Sahara T, Ohgiya S, Gomi K, Oikawa H (2011) Total biosynthesis of diterpene aphidicolin, a specific inhibitor of DNA polymerase a: Heterologous expression of four biosynthetic genes in Aspergillus oryzae. Biosci Biotechnol Biochem 75:1813–1817.  https://doi.org/10.1271/bbb.110366 CrossRefPubMedGoogle Scholar
  32. Funa N, Awakawa T, Horinouchi S (2007) Pentaketide resorcylic acid synthesis by type III polyketide synthase from Neurospora crassa. J Biol Chem 282:14476–14481.  https://doi.org/10.1074/jbc.M701239200 CrossRefPubMedGoogle Scholar
  33. Gagne SJ, Stout JM, Liu E, Boubakir Z, Clark SM, Page JE (2012) Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides. Proc Natl Acad Sci USA 109:12811–12816.  https://doi.org/10.1073/pnas.1200330109 CrossRefPubMedGoogle Scholar
  34. Gagunashvili AN, Davidsson SP, Jónsson ZO, Andrésson OS (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 CrossRefPubMedGoogle Scholar
  35. Gokulan K, O’Leary SE, Russell WK, Russell DH, Lalgondar M, Begley TP, Ioerger TR, Sacchettini JC (2013) Crystal structure of Mycobacterium tuberculosis polyketide synthase 11 (PKS11) reveals intermediates in the synthesis of methyl-branched alkylpyrones. J Biol Chem 288:16484–16494.  https://doi.org/10.1074/jbc.M113.468892 CrossRefPubMedPubMedCentralGoogle Scholar
  36. Goyal A, Saxena P, Rahman A, Singh PK, Kasbekar DP, Gokhale RS, Sankaranarayanan R (2008) Structural insights into biosynthesis of resorcinolic lipids by a type III polyketide synthase in Neurospora crassa. J Struct Biol 162:411–421.  https://doi.org/10.1016/j.jsb.2008.02.009 CrossRefPubMedGoogle Scholar
  37. Grube M, Berg G, Andrésson ÓS, Dyer PS, Miao VPW, Vilhelmsson O (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.ch9 CrossRefGoogle Scholar
  38. Guex N, Peitsch MC (1997) SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18:2714–2723.  https://doi.org/10.1002/elps.1150181505 CrossRefPubMedGoogle Scholar
  39. Hashimoto M, Nonaka T, Fujii I (2014) Fungal type III polyketide synthases. Nat Prod Rep 31:1306–1317.  https://doi.org/10.1039/C4NP00096J CrossRefPubMedGoogle Scholar
  40. He Y, Cox RJ (2016) The molecular steps in citrinin biosynthesis in fungi. Chem Sci 7:2119–2127.  https://doi.org/10.1039/C5SC04027B CrossRefPubMedGoogle Scholar
  41. He J, Hertweck C (2004) Biosynthetic origin of the rare nitroaryl moiety of the polyketide antibiotic aureothin: involvement of an unprecedented N-oxygenase. J Am Chem Soc 126:3694–3695.  https://doi.org/10.1021/ja039328t CrossRefPubMedGoogle Scholar
  42. Herbst DA, Townsend CA, Maier T (2018) The architectures of iterative type I PKS and FAS. Nat Prod Rep 35:1046–1069.  https://doi.org/10.1039/C8NP00039E CrossRefPubMedPubMedCentralGoogle Scholar
  43. Jeya M, Kim TS, Tiwari MK, Li J, Zhao H, Lee JK (2010) The Botrytis cinerea type III polyketide synthase shows unprecedented high catalytic efficiency toward long chain acyl-CoAs. Mol BioSyst 8:2864–2867.  https://doi.org/10.1039/c2mb25282a CrossRefGoogle Scholar
  44. Jez JM, Austin MB, Ferrer J, Bowman ME, Schröder J, Noel JP (2000) Structural control of polyketide formation in plant-specific polyketide synthases. Chem Biol 7:919–930.  https://doi.org/10.1016/S1074-5521(00)00041-7 CrossRefPubMedGoogle Scholar
  45. Kirimura K, Watanabe S, Kobayashi K (2016) Heterologous gene expression and functional analysis of a type III polyketide synthase from Aspergillus niger NRRL 328. Biochem Biophys Res Commun 473:1106–1110.  https://doi.org/10.1016/j.bbrc.2016.04.023 CrossRefPubMedGoogle Scholar
  46. Kumar S, Stecher G, Tamura K (2016) MEGA7: molecular evolutionary genetics analysis version 7.0 for bigger datasets. Mol Biol Evol 33:1870–1874.  https://doi.org/10.1093/molbev/msw054 CrossRefPubMedPubMedCentralGoogle Scholar
  47. Li J, Luo Y, Lee JK, Zhao H (2011) Cloning and characterization of a type III polyketide synthase from Aspergillus niger. Bioorg Med Chem Lett 21:6085–6089.  https://doi.org/10.1016/j.bmcl.2011.08.058 CrossRefPubMedGoogle Scholar
  48. Lutzoni F, Miadlikowska J (2009) Lichens. Curr Biol 19:R502–R503.  https://doi.org/10.1016/j.cub.2009.04.034 CrossRefPubMedGoogle Scholar
  49. Magarvey NA, Beck ZQ, Golakoti T, Ding Y, Huber U, Hemscheidt TK, Abelson D, Moore RE, Sherman DH (2006) Biosynthetic characterization and chemoenzymatic assembly of the cryptophycins. Potent anticancer agents from cyanobionts. ACS Chem. Biol 1:766–779.  https://doi.org/10.1021/cb6004307 CrossRefPubMedGoogle Scholar
  50. Matsuda Y, Awakawa T, Abe I (2013) Reconstituted biosynthesis of fungal meroterpenoid andrastin A. Tetrahedron 69:8199–9204.  https://doi.org/10.1016/j.tet.2013.07.029 CrossRefGoogle Scholar
  51. Matsuda Y, Iwabuchi T, Wakimoto T, Awakawa T, Abe I (2015) Uncovering the unusual D-ring construction in terretonin biosynthesis by collaboration of a multifunctional cytochrome p450 and a unique isomerase. J Am Chem Soc 137:3393–3401.  https://doi.org/10.1021/jacs.5b00570 CrossRefPubMedGoogle Scholar
  52. Matsuda Y, Iwabuchi T, Fujimoto T, Awakawa T, Nakashima Y, Mori T, Zhang H, Hayashi F, Abe I (2016) Discovery of key dioxygenases that diverged the paraherquonin and acetoxydehydroaustin pathways in Penicillium brasilianum. J Am Chem Soc 138:12671–12677.  https://doi.org/10.1021/jacs.6b08424 CrossRefPubMedGoogle Scholar
  53. Matsuda Y, Bai T, Phippen CBW, Nødvig CS, Kjærbølling I, Vesth TC, Andersen MR, Mortensen UH, Gotfredsen CH, Abe I, Larsen TO (2018) Novofumigatonin biosynthesis involves a non-heme iron-dependent endoperoxide isomerase for orthoester formation. Nat Commun 9:2587.  https://doi.org/10.1038/s41467-018-04983-2 CrossRefPubMedPubMedCentralGoogle Scholar
  54. Meslet-Cladière L, Delage L, Leroux CJ, Goulitguer S, Leblanc C, Creis E, Gall EA, Stiger-Pouvreau V, Czjzek M, Potin P (2013) Structure/function analysis of a type III polyketide synthase in the brown alga Ectocarpus siliculosus reveals a biochemical pathway in phlorotannin monomer biosynthesis. Plant Cell 25:3089–3103.  https://doi.org/10.1105/tpc.113.111336 CrossRefPubMedPubMedCentralGoogle Scholar
  55. Miyanaga A, Funa N, Awakawa T, Horinouchi S (2008) Direct transfer of starter substrates from type I fatty acid synthase to type III polyketide synthases in phenolic lipid synthesis. Proc Natl Acad Sci USA 105:871–876.  https://doi.org/10.1073/pnas.0709819105 CrossRefPubMedGoogle Scholar
  56. Mori T, Yang D, Matsui T, Hashimoto M, Morita H, Fujii I, Abe I (2015) Structural basis for the formation of acylalkylpyrones from two β-ketoacyl units by the fungal type III polyketide synthase CsyB. J Biol Chem 290:5214–5225.  https://doi.org/10.1074/jbc.M114.626416 CrossRefPubMedPubMedCentralGoogle Scholar
  57. Morita H, Kondo S, Oguro S, Noguchi H, Sugio S, Abe I, Kohno T (2007) Structural insight into chain-length control and product specificity of pentaketide chromone synthase from Aloe arborescens. Chem Biol 14:359–369.  https://doi.org/10.1016/j.chembiol.2007.02.003 CrossRefPubMedGoogle Scholar
  58. Morita H, Wanibuchi K, Nii H, Kato R, Sugio S, Abe I (2010) Structural basis for the one-pot formation of the diarylheptanoid scaffold by curcuminoid synthase from Oryza sativa. Proc Natl Acad Sci USA 107:19778–19783.  https://doi.org/10.1073/pnas.1011499107 CrossRefPubMedGoogle Scholar
  59. Morita M, Yamashita M, Shi SP, Wakimoto T, Kondo S, Kato R, Sugio S, Kohno T, Abe I (2011) Synthesis of unnatural alkaloid scaffolds by exploiting plant polyketide synthase. Proc Natl Acad Sci USA 108:13504–13509.  https://doi.org/10.1073/pnas.1107782108 CrossRefPubMedGoogle Scholar
  60. Muggia L, Grube M (2010) Type III polyketide synthases in lichen mycobionts. Fungal Biol 114:379–385.  https://doi.org/10.1016/j.funbio.2010.03.001 CrossRefPubMedGoogle Scholar
  61. Nash TH III (2008) Lichen biology, 2nd edn. Cambridge University Press, CambridgeCrossRefGoogle Scholar
  62. Nofiani R, de Mattos-Shipley K, Lebe KE, Han LC, Iqbal Z, Bailey AM, Willis CL, Simpson TJ, Cox RJ (2018) Strobilurin biosynthesis in Basidiomycete fungi. Nat Commun 9:3940.  https://doi.org/10.1038/s41467-018-06202-4 CrossRefPubMedPubMedCentralGoogle Scholar
  63. Olano C, Wilkinson B, Sánchez C, Moss SJ, Sheridan R, Math V, Weston AJ, Braña AF, Martin CJ, Oliynyk M, Méndez C, Leadlay PF, Salas JA (2004) Biosynthesis of the angiogenesis inhibitor borrelidin by Streptomyces parvulus Tü4055: cluster analysis and assignment of functions. Chem Biol 11:87–97.  https://doi.org/10.1016/j.chembiol.2003.12.018 CrossRefPubMedGoogle Scholar
  64. Polovinka MP, Komarova NI, Korchagina DV, Sokolov DN, Luzina OA, Vlasenko NG, Malyuga AA, Romanova EV, Salakhutdinov NF (2012) Secondary metabolites of the lichen Cladonia stellaris. Chem Nat Compd 48:392–395.  https://doi.org/10.1007/s10600-012-0259-4 CrossRefGoogle Scholar
  65. Ramakrishnan D, Tiwari MK, Manoharan G, Sairam T, Thangamani R, Lee JK, Marimuthu J (2018) Molecular characterization of two alkylresorcylic acid synthases from Sordariomycetes fungi. Enzyme Microb Technol 115:16–22.  https://doi.org/10.1016/j.enzmictec.2018.04.006 CrossRefPubMedGoogle Scholar
  66. Robbins T, Liu YC, Cane DE, Khosla C (2016) Structure and mechanism of assembly line polyketide synthases. Curr Opin Struct Biol 41:10–18.  https://doi.org/10.1016/j.sbi.2016.05.009 CrossRefPubMedPubMedCentralGoogle Scholar
  67. Rubin-Pitel SB, Zhang H, Vu T, Brunzelle JS, Zhao H, Nair SK (2008) Distinct structural elements dictate the specificity of the type III pentaketide synthase from Neurospora crassa. Chem Biol 15:1079–1090.  https://doi.org/10.1016/j.chembiol.2008.08.011 CrossRefPubMedPubMedCentralGoogle Scholar
  68. Saitou N, Nei M (1987) The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol 4:406–425.  https://doi.org/10.1093/oxfordjournals.molbev.a040454 CrossRefPubMedGoogle Scholar
  69. Sankaranarayanan R, Saxena P, Marathe UB, Gokhale RS, Shanmugam VM, Rukmini R (2004) A novel tunnel in mycobacterial type III polyketide synthase reveals the structural basis for generating diverse metabolites. Nat Struct Mol Biol 11:894–900.  https://doi.org/10.1038/nsmb809 CrossRefPubMedGoogle Scholar
  70. Satou R, Miyanaga A, Ozawa H, Funa N, Katsuyama Y, Miyazono K, Tanokura M, Ohnishi Y, Horinouchi S (2013) Structural basis for cyclization specificity of two Azotobacter type III polyketide synthases: a single amino acid substitution reverses their cyclization specificity. J Biol Chem 288:34146–34157.  https://doi.org/10.1074/jbc.M113.487272 CrossRefPubMedPubMedCentralGoogle Scholar
  71. Schor R, Schotte C, Wibberg D, Kalinowski J, Cox RJ (2018) Three previously unrecognized classes of biosynthetic enzymes revealed during the production of xenovulene A. Nat Commun 9:1963.  https://doi.org/10.1038/s41467-018-04364-9 CrossRefPubMedPubMedCentralGoogle Scholar
  72. Seshime Y, Juvvadi PR, Fujii I, Kitamoto K (2005) Discovery of a novel superfamily of type III polyketide synthases in Aspergillus oryzae. Biochem Biophys Res Commun 331:253–260.  https://doi.org/10.1016/j.bbrc.2005.03.160 CrossRefPubMedGoogle Scholar
  73. Shi SP, Wanibuchi K, Morita H, Endo K, Noguchi H, Abe I (2009) Enzymatic formation of unnatural novel chalcone, stilbene, and benzophenone scaffolds by plant type III polyketide synthases. Org Lett 11:551–554.  https://doi.org/10.1021/ol802606w CrossRefPubMedGoogle Scholar
  74. Shibata S, Chiang HC (1965) The structures of cryptochlorophaeic acid and merochlorophaeic acid. Phytochemistry 4:133–139.  https://doi.org/10.1016/S0031-9422(00)86155-5 CrossRefGoogle Scholar
  75. Shimizu Y, Ogata H, Goto S (2017) Type III polyketide synthases: functional classification and phylogenetics. ChemBioChem 18:50–65.  https://doi.org/10.1002/cbic.201600522 CrossRefPubMedGoogle Scholar
  76. Shirley BW, Kubasek WL, Storz G, Bruggemann E, Koornneef M, Ausubel FM, Goodman HM (1995) Analysis of Arabidopsis mutants deficient in flavonoid biosynthesis. Plant J 8:659–671.  https://doi.org/10.1046/j.1365-313X.1995.08050659.x CrossRefPubMedGoogle Scholar
  77. Staunton J, Weissman KJ (2001) Polyketide biosynthesis: A millennium review. Nat Prod Rep 18:380–416.  https://doi.org/10.1039/a909079g CrossRefPubMedGoogle Scholar
  78. Stenroos S, Pino-Bodas R, Weckman D, Ahti T (2015) Phylogeny of Cladonia uncialis (Cladoniaceae, Lecanoromycetes) and its allies. Lichenologist 47:215–231.  https://doi.org/10.1017/S0024282915000183 CrossRefGoogle Scholar
  79. Stout JM, Boubakir Z, Ambrose SJ, Purves RW, Page JE (2012) The hexanoyl-CoA precursor for cannabinoid biosynthesis is formed by an acyl-activating enzyme in Cannabis sativa trichomes. Plant J 71:353–365.  https://doi.org/10.1111/j.1365-313X.2012.04949.x CrossRefPubMedGoogle Scholar
  80. Studzińska-Sroka E, Hołderna-Kędzia E, Galanty A, Bylka W, Kacprzak K, Ćwiklińska K (2015) In vitro antimicrobial activity of extracts and compounds isolated from Cladonia uncialis. Nat Prod Res 29:2302–2307.  https://doi.org/10.1080/14786419.2015.1005616 CrossRefPubMedGoogle Scholar
  81. Sun L, Wang S, Zhang S, Yu D, Qin Y, Huang H, Wang W, Zhan J (2016) Identification of a type III polyketide synthase involved in the biosynthesis of spirolaxine. Appl Microbiol Biotechnol 100:7103–7113.  https://doi.org/10.1007/s00253-016-7444-5 CrossRefPubMedGoogle Scholar
  82. Tang GL, Cheng YQ, Shen B (2004) Leinamycin biosynthesis revealing unprecedented architectural complexity for a hybrid polyketide synthase and nonribosomal peptide synthetase. Chem Biol 11:33–45.  https://doi.org/10.1016/j.chembiol.2003.12.014 CrossRefPubMedGoogle Scholar
  83. Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequencing weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680.  https://doi.org/10.1093/nar/22.22.4673 CrossRefPubMedPubMedCentralGoogle Scholar
  84. Tian W, Chen C, Lei X, Zhao J, Liang J (2018) CASTp 3.0: computed atlas of surface topology of proteins. Nucleic Acids Res 46:W363–W367.  https://doi.org/10.1093/nar/gky473 CrossRefPubMedPubMedCentralGoogle Scholar
  85. Wang Y, Neng Z, Xiaolong Y, Mei H, Hur JS, Yuming Y, Juan W (2016) Heterologous transcription of a polyketide synthase gene from the lichen forming fungus Usnea longissima. Res J Biotechnol 11:16–21Google Scholar
  86. Wang Y, Geng C, Yuan X, Hua M, Tian F, Li C (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 CrossRefPubMedPubMedCentralGoogle Scholar
  87. Wanibuchi K, Morita H, Noguchi H, Abe I (2011) Enzymatic formation of an aromatic dodecaketide by engineered plant polyketide synthase. Biorg Med Chem Lett 21:2083–2086.  https://doi.org/10.1016/j.bmcl.2011.01.135 CrossRefGoogle Scholar
  88. Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bordoli L, Lepore R, Schwede T (2018) SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res 46:W296–W303.  https://doi.org/10.1093/nar/gky427 CrossRefPubMedPubMedCentralGoogle Scholar
  89. Yan H, Sun L, Huang J, Qiu Y, Xu F, Yan R, Zhu D, Wang W, Zhan J (2018) Identification and heterologous reconstitution of a 5-alk(en)ylresorcinol synthase from endophytic fungus Shiraia sp. Slf14. J Microbiol 56:805–812.  https://doi.org/10.1007/s12275-018-8278-x CrossRefPubMedGoogle Scholar
  90. Yu D, Zeng J, Chen D, Zhan J (2010) Characterization and reconstitution of a new fungal type III polyketide synthase from Aspergillus oryzae. Enzyme Microb Technol 46:575–580.  https://doi.org/10.1016/j.enzmictec.2010.02.011 CrossRefGoogle Scholar
  91. Yu D, Xu F, Zeng J, Zhan J (2012) Type III polyketide synthases in natural product biosynthesis. IUBMB Life 64:285–295.  https://doi.org/10.1002/iub.1005 CrossRefPubMedGoogle Scholar
  92. 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 CrossRefPubMedPubMedCentralGoogle Scholar
  93. Zuckerkandl E, Pauling L (1965) Evolutionary divergence and convergence in proteins. In: Bryson V, Vogel HJ (eds) Evolving genes and proteins. Academic Press, New York, pp 97–166.  https://doi.org/10.1016/B978-1-4832-2734-4.50017-6 CrossRefGoogle Scholar

Copyright information

© German Mycological Society and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of ManitobaWinnipegCanada
  2. 2.Lawrence Berkeley National LaboratoryJoint BioEnergy InstituteEmeryvilleUSA

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