The genome of the Tiger Milk mushroom, Lignosus rhinocerotis, provides insights into the genetic basis of its medicinal properties

BMC Genomics

Nget-Hong Tan²  Chon-Seng Tan⁴  Szu-Ting Ng⁵  Shin-Yee Fung²  Mohd Firdaus-Raih¹  Yit-Heng Chooi³  Hui-Yeng Y Yap² 

[1] School of Biosciences and Biotechnology, Faculty of Science and Technology and Institute of Systems Biology, Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Malaysia;Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia;Plant Sciences Division, Research School of Biology, The Australian National University, Canberra 0200, Australia;Malaysian Agricultural Research and Development Institute (MARDI), 43400 Serdang, Selangor, Malaysia;Ligno Biotech Sdn. Bhd., 43300 Balakong Jaya, Selangor, Malaysia

关键词: Cytochrome P450 superfamily;    Carbohydrate-active enzymes;    Secondary metabolism;    Phylogeny;    Genome;    Lignosus rhinocerotis;   

Others  :  1216361
DOI  :  10.1186/1471-2164-15-635

 received in 2014-02-17, accepted in 2014-07-23,  发布年份 2014

【 摘 要 】

Background

The sclerotium of Lignosus rhinocerotis (Cooke) Ryvarden or Tiger milk mushroom (Polyporales, Basidiomycota) is a valuable folk medicine for indigenous peoples in Southeast Asia. Despite the increasing interest in this ethnobotanical mushroom, very little is known about the molecular and genetic basis of its medicinal and nutraceutical properties.

Results

The de novo assembled 34.3 Mb L. rhinocerotis genome encodes 10,742 putative genes with 84.30% of them having detectable sequence similarities to others available in public databases. Phylogenetic analysis revealed a close evolutionary relationship of L. rhinocerotis to Ganoderma lucidum, Dichomitus squalens, and Trametes versicolor in the core polyporoid clade. The L. rhinocerotis genome encodes a repertoire of enzymes engaged in carbohydrate and glycoconjugate metabolism, along with cytochrome P450s, putative bioactive proteins (lectins and fungal immunomodulatory proteins) and laccases. Other genes annotated include those encoding key enzymes for secondary metabolite biosynthesis, including those from polyketide, nonribosomal peptide, and triterpenoid pathways. Among them, the L. rhinocerotis genome is particularly enriched with sesquiterpenoid biosynthesis genes.

Conclusions

The genome content of L. rhinocerotis provides insights into the genetic basis of its reported medicinal properties as well as serving as a platform to further characterize putative bioactive proteins and secondary metabolite pathway enzymes and as a reference for comparative genomics of polyporoid fungi.

【 授权许可】

   
2014 Yap et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Lee SS, Chang YS: Ethnomycology. In Malaysian Fungal Diversity. Edited by Jones EBG, Hyde KD, Sabaratnam V. Malaysia: Mushroom Research Centre, University of Malaya and Natural Resources and Environment, Malaysia; 2007:307-317.
• [2]Willetts HJ, Bullock S: Developmental biology of sclerotia. Mycol Res 1992, 96:801-816.
• [3]Cunningham GH: Polyporaceae of New Zealand. Bull New Zealand Dept Sci Industr Res 1965, 164:1-304.
• [4]Tan CS, Ng ST, Vikineswary S, Lo EP, Tee CS: Genetic markers for identification of a Malaysian medicinal mushroom Lignosus rhinocerus (Cendawan susu rimau). Acta Hortic 2010, 859:161-167.
• [5]Yap YHY, Tan NH, Fung SY, Aziz AA, Tan CS, Ng ST: Nutrient composition, antioxidant properties, and anti-proliferative activity of Lignosus rhinocerus Cooke sclerotium. J Sci Food Agric 2013, 9:2945-2952.
• [6]Lai CKM, Wong KH, Cheung PCK: Antiproliferative effects of sclerotial polysaccharides from Polyporus rhinocerus Cooke (Aphyllophoromycetideae) on different kinds of leukemic cells. Int J Med Mushrooms 2008, 10:255-264.
• [7]Lee ML, Tan NH, Fung SY, Tan CS, Ng ST: The antiproliferative activity of sclerotia of Lignosus rhinocerus (Tiger Milk Mushroom). Evid Based Complement Alternat Med 2012, 2012:697603.
• [8]Wong KH, Lai CKM, Cheung PCK: Immunomodulatory activities of mushroom sclerotial polysaccharides. Food Hydrocoll 2011, 25:150-158.
• [9]Gao S, Lai CKM, Cheung PCK: Nondigestible carbohydrates isolated from medicinal mushroom sclerotia as novel prebiotics. Int J Med Mushrooms 2009, 11:1-8.
• [10]Galagan JE, Henn MR, Ma LJ, Cuomo CA, Birren B: Genomics of the fungal kingdom: insights into eukaryotic biology. Genome Res 2005, 15:1620-1631.
• [11]Chen S, Xu J, Liu C, Zhu Y, Nelson DR, Zhou S, Li C, Wang L, Guo X, Sun Y, Luo H, Li Y, Song J, Henrissat B, Levasseur A, Qian J, Li J, Luo X, Shi L, He L, Xiang L, Xu X, Niu Y, Li Q, Han MV, Yan H, Zhang J, Chen H, Lv A, Wang Z, et al.: Genome sequence of the model medicinal mushroom Ganoderma lucidum. Nat Commun 2012, 3:913.
• [12]Liu D, Gong J, Dai W, Kang X, Huang Z, Zhang HM, Liu W, Liu L, Ma J, Xia Z, Chen Y, Chen YW, Wang D, Ni P, Guo AY, Xiong X: The genome of Ganoderma lucidum provides insights into triterpenes biosynthesis and wood degradation. PLoS ONE 2012, 7:e36146.
• [13]Bao D, Gong M, Zheng H, Chen M, Zhang L, Wang H, Jiang J, Wu L, Zhu Y, Zhu G, Zhou Y, Li C, Wang S, Zhao Y, Zhao G, Tan Q: Sequencing and comparative analysis of the straw mushroom (Volvariella volvacea) genome. PLoS ONE 2013, 8:e58294.
• [14]Foulongne-Oriol M, Murat C, Castanera R, Ramírez L, Sonnenberg AS: Genome-wide survey of repetitive DNA elements in the button mushroom Agaricus bisporus. Fungal Genet Biol 2013, 55:6-21.
• [15]Floudas D, Binder M, Riley R, Barry K, Blanchette RA, Henrissat B, Martínez AT, Otillar R, Spatafora JW, Yadav JS, Aerts A, Benoit I, Boyd A, Carlson A, Copeland A, Coutinho PM, de Vries RP, Ferreira P, Findley K, Foster B, Gaskell J, Glotzer D, Górecki P, Heitman J, Hesse C, Hori C, Igarashi K, Jurgens JA, Kallen N, Kersten P, et al.: The Paleozoic origin of enzymatic lignin decomposition reconstructed from 31 fungal genomes. Science 2012, 336:1715-1719.
• [16]Zheng W, Huang L, Huang J, Wang X, Chen X, Zhao J, Guo J, Zhuang H, Qiu C, Liu J, Liu H, Huang X, Pei G, Zhan G, Tang C, Cheng Y, Liu M, Zhang J, Zhao Z, Zhang S, Han Q, Han D, Zhang H, Zhao J, Gao X, Wang J, Ni P, Dong W, Yang L, Yang H, et al.: High genome heterozygosity and endemic genetic recombination in the wheat stripe rust fungus. Nat Commun 2013, 4:2673.
• [17]Kotera M, Okuno Y, Hattori M, Goto S, Kanehisa M: Computational assignment of the EC numbers for genomic-scale analysis of enzymatic reactions. J Am Chem Soc 2004, 126:16487-16498.
• [18]Kuramae EE, Robert V, Snel B, Weiss M, Boekhout T: Phylogenomics reveal a robust fungal tree of life. FEMS Yeast Res 2006, 6:1213-1220.
• [19]Binder M, Justo A, Riley R, Salamov A, Lopez-Giraldez F, Sjokvist E, Copeland A, Foster B, Sun H, Larsson E, Larsson KH, Townsend J, Grigoriev IV, Hibbett DS: Phylogenetic and phylogenomic overview of the Polyporales. Mycologia 2013, 105:1350-1373.
• [20]Wong KH, Cheung PCK: Sclerotia: Emerging Functional Food Derived from Mushrooms. In Mushrooms as Functional Foods. Edited by Cheung PCK. New Jersey: John Wiley & Sons, Inc; 2009:111-146.
• [21]Crešnar B, Petrič S: Cytochrome P450 enzymes in the fungal kingdom. Biochim Biophys Acta 1814, 2011:29-35.
• [22]Nelson DR: The cytochrome P450 homepage. Hum Genomics 2009, 4:59-65.
• [23]Doddapaneni H, Yadav JS: Differential regulation and xenobiotic induction of tandem P450 monooxygenase genes pc-1 (CYP63A1) and pc-2 (CYP63A2) in the white-rot fungus Phanerochaete chrysosporium. Appl Microbiol Biotechnol 2004, 65:559-665.
• [24]Keller NP, Turner G, Bennett JW: Fungal secondary metabolism - from biochemistry to genomics. Nat Rev Microbiol 2005, 3:937-947.
• [25]Ishiuchi K, Nakazawa T, Ookuma T, Sugimoto S, Sato M, Tsunematsu Y, Ishikawa N, Noguchi H, Hotta K, Moriya H, Watanabe K: Establishing a new methodology for genome mining and biosynthesis of polyketides and peptides through yeast molecular genetics. Chembiochem 2012, 13:846-854.
• [26]Shi L, Ren A, Mu D, Zhao M: Current progress in the study on biosynthesis and regulation of ganoderic acids. Appl Microbiol Biotechnol 2010, 88:1243-1251.
• [27]Novak R, Shlaes DM: The pleuromutilin antibiotics: a new class for human use. Curr Opin Investig Drugs 2010, 11:182-191.
• [28]Schobert R, Knauer S, Seibt S, Biersack B: Anticancer active illudins: recent developments of a potent alkylating compound class. Curr Med Chem 2011, 18:790-807.
• [29]Corey EJ, Matsuda SP, Bartel B: Isolation of an Arabidopsis thaliana gene encoding cycloartenol synthase by functional expression in a yeast mutant lacking lanosterol synthase by the use of a chromatographic screen. Proc Natl Acad Sci U S A 1993, 90:11628-11632.
• [30]Kramer R, Abraham W-R: Volatile sesquiterpenes from fungi: what are they good for? Phytochem Rev 2012, 11:15-37.
• [31]Wawrzyn GT, Quin MB, Choudhary S, López-Gallego F, Schmidt-Dannert C: Draft genome of Omphalotus olearius provides a predictive framework for sesquiterpenoid natural product biosynthesis in Basidiomycota. Chem Biol 2012, 19:772-783.
• [32]Nierman WC, Pain A, Anderson MJ, Wortman JR, Kim HS, Arroyo J, Berriman M, Abe K, Archer DB, Bermejo C, Bennett J, Bowyer P, Chen D, Collins M, Coulsen R, Davies R, Dyer PS, Farman M, Fedorova N, Fedorova N, Feldblyum TV, Fischer R, Fosker N, Fraser A, García JL, García MJ, Goble A, Goldman GH, Gomi K, Griffith-Jones S, et al.: Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature 2005, 438:1151-1156.
• [33]Xu Z, Chen X, Zhong Z, Chen L, Wang Y: Ganoderma lucidum polysaccharides: immunomodulation and potential anti-tumor activities. Am J Chin Med 2011, 39:15-27.
• [34]Xu X, Yan H, Chen J, Zhang X: Bioactive proteins from mushrooms. Biotechnol Adv 2011, 29:667-674.
• [35]Kino K, Yamashita A, Yamaoka K, Watanabe J, Tanaka S, Ko K, Shimizu K, Tsunoo H: Isolation and characterization of a new immunomodulatory protein, ling zhi-8 (LZ-8), from Ganoderma lucidium. J Biol Chem 1989, 264:472-478.
• [36]Wu CT, Lin TY, Hsu HY, Sheu F, Ho CM, Chen EI: Ling Zhi-8 mediates p53-dependent growth arrest of lung cancer cells proliferation via the ribosomal protein S7-MDM2-p53 pathway. Carcinogenesis 2011, 32:1890-1896.
• [37]Paaventhan P, Joseph JS, Seow SV, Vaday S, Robinson H, Chua KY, Kolatkar PR: A 1.7A structure of Fve, a member of the new fungal immunomodulatory protein family. J Mol Biol 2003, 332:461-470.
• [38]Cota-Sánchez JH, Remarchuk K, Ubayasena K: Ready-to-use DNA extracted with a CTAB method adapted for herbarium specimens and mucilaginous plant tissue. Plant Mol Biol Rep 2006, 24:161-167.
• [39]Li R, Zhu H, Ruan J, Qian W, Fang X, Shi Z, Li Y, Li S, Shan G, Kristiansen K, Li S, Yang H, Wang J, Wang J: De novo assembly of human genomes with massively parallel short read sequencing. Genome Res 2010, 20:265-272.
• [40]Stanke M, Waack S: Gene prediction with a hidden Markov model and a new intron submodel. Bioinformatics 2003, 19(Suppl 2):ii215-ii225.
• [41]Borodovsky M, Lomsadze A: Eukaryotic gene prediction using GeneMark.hmm.-E and GeneMark-ES. Curr Protoc Bioinformatics 2011, Chapter 4:1-10.
• [42]Korf I: Gene finding in novel genomes. BMC Bioinformatics 2004, 5:59.
• [43]Jurka J, Kapitonov VV, Pavlicek A, Klonowski P, Kohany O, Walichiewicz J: Repbase update, a database of eukaryotic repetitive elements. Cytogenet Genome Res 2005, 110:462-467.
• [44]Benson G: Tandem repeats finder: a program to analyze DNA sequences. Nucleic Acids Res 1999, 27:573-580.
• [45]Lagesen K, Hallin P, Rodland EA, Staerfeldt HH, Rognes T, Ussery DW: RNAmmer: consistent and rapid annotation of ribosomal RNA genes. Nucleic Acids Res 2007, 35:3100-3108.
• [46]Schattner P, Brooks AN, Lowe TM: The tRNAscan-SE, snoscan and snoGPS web servers for the detection of tRNAs and snoRNAs. Nucleic Acids Res 2005, 33:W686-W689.
• [47]Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G: Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 2000, 25:25-29.
• [48]Koonin EV, Fedorova ND, Jackson JD, Jacobs AR, Krylov DM, Makarova KS, Mazumder R, Mekhedov SL, Nikolskaya AN, Rao BS, Rogozin IB, Smirnov S, Sorokin AV, Sverdlov AV, Vasudevan S, Wolf YI, Yin JJ, Natale DA: A comprehensive evolutionary classification of proteins encoded in complete eukaryotic genomes. Genome Biol 2004, 5:R7.
• [49]Kanehisa M, Goto S, Kawashima S, Okuno Y, Hattori M: The KEGG resource for deciphering the genome. Nucleic Acids Res 2004, 32:D277-D280.
• [50]Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG: The ClustalX windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 1997, 25:4876-4882.
• [51]Xia X: DAMBE5: a comprehensive software package for data analysis in molecular biology and evolution. Mol Biol Evol 2013, 30:1720-1728.
• [52]Castresana J: Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. Mol Biol Evol 2000, 17:540-552.
• [53]Abascal F, Zardoya R, Posada D: ProtTest: selection of best-fit models of protein evolution. Bioinformatics 2005, 21:2104-2105.
• [54]Felsenstein J: Inferring phylogenies from protein sequences by parsimony, distance, and likelihood methods. Methods Enzymol 1996, 266:418-427.
• [55]Schmidt HA, Strimmer K, Vingron M, von Haeseler A: TREE-PUZZLE: maximum likelihood phylogenetic analysis using quartets and parallel computing. Bioinformatics 2002, 18:502-504.
• [56]Müller T, Vingron M: Modeling amino acid replacement. J Comput Biol 2000, 7:761-776.
• [57]Huelsenbeck JP, Ronquist F: MRBAYES: Bayesian inference of phylogenetic trees. Bioinformatics 2001, 17:754-755.
• [58]Kumar S, Tamura K, Nei M: MEGA3: integrated software for molecular evolutionary genetics analysis and sequence alignment. Brief Bioinform 2004, 5:150-163.
• [59]Cantarel BL, Coutinho PM, Rancurel C, Bernard T, Lombard V, Henrissat B: The carbohydrate-active EnZymes database (CAZy): an expert resource for glycogenomics. Nucleic Acids Res 2009, 37:D233-D238.
• [60]Khaldi N, Seifuddin FT, Turner G, Haft D, Nierman WC, Wolfe KH, Fedorova ND: SMURF: genomic mapping of fungal secondary metabolite clusters. Fungal Genet Biol 2010, 47:736-741.
• [61]Blin K, Medema MH, Kazempour D, Fischbach MA, Breitling R, Takano E, Weber T: antiSMASH 2.0 — a versatile platform for genome mining of secondary metabolite producers. Nucleic Acids Res 2013, 41:W204-W212.