Secondary Metabolites from Higher Fungi: Discovery, Bioactivity, and Bioproduction

Chapter
Part of the Advances in Biochemical Engineering / Biotechnology book series (ABE, volume 113)

Abstract

Medicinal higher fungi such as Cordyceps sinensis and Ganoderma lucidum have been used as an alternative medicine remedy to promote health and longevity for people in China and other regions of the world since ancient times. Nowadays there is an increasing public interest in the secondary metabolites of those higher fungi for discovering new drugs or lead compounds. Current research in drug discovery from medicinal higher fungi involves a multifaceted approach combining mycological, biochemical, pharmacological, metabolic, biosynthetic and molecular techniques. In recent years, many new secondary metabolites from higher fungi have been isolated and are more likely to provide lead compounds for new drug discovery, which may include chemopreventive agents possessing the bioactivity of immunomodulatory, anticancer, etc. However, numerous challenges of secondary metabolites from higher fungi are encountered including bioseparation, identification, biosynthetic metabolism, and screening model issues, etc. Commercial production of secondary metabolites from medicinal mushrooms is still limited mainly due to less information about secondary metabolism and its regulation. Strategies for enhancing secondary metabolite production by medicinal mushroom fermentation include two-stage cultivation combining liquid fermentation and static culture, two-stage dissolved oxygen control, etc. Purification of bioactive secondary metabolites, such as ganoderic acids from G. lucidum, is also very important to pharmacological study and future pharmaceutical application. This review outlines typical examples of the discovery, bioactivity, and bioproduction of secondary metabolites of higher fungi origin.

Keywords

Bioactive compound Fermentation production Higher fungi Medicinal mushroom Physiological and pharmacological activity 

Abbreviations

ABTS

2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonate)

Abu

Aminobutyric acid

Aib

α-Aminoisobutyric acid

Ala

Alanine

BHA

Butyl hydroxyanisole

COX

Cyclooxygenase

DHNM

Dihydroxynaphthalene melanin

DMBA

7,12-Dimethylbenz[α]anthracene

DPPH

2,2-Diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl

EBV-EA

Epstein–Barr virus early antigen

EC50

50%Effective concentration

ESI-MS

Electrospray ionization mass spectrometry

Glc

Glucose

GLP

Ganoderma lucidum peptide

Gly

Glycine

HPLC

High-performance liquid chromatography

HRMS

High-resolution mass spectrometry

HyLeu

Hydroxyleucine

IC50

50% Inhibitory concentration value

kDa

Kilo Dalton

Leu

Leucine

Lxx

N-methylleucine/N-methylisoleucine/N-methylalloisoleucine

MePro

Methylproline

mg

Milligram

mL

Milliliter

mmol

Millimolar

NE

Norepinephrine

NmePh

N-Methylphenylalanine

NmeVal

N-Methylvaline

Phe

Phenylalanine

Pro

Proline

PTP1B

Protein tyrosine phosphatase 1B

PTP1B

Protein tyrosine phosphatase 1B

RP-HPLC

Reversed phase HPLC

TCM

Traditional Chinese medicine

TPA

12-O-Tetradecanoylphorbol-13-acetate

UV

Ultraviolet

Val

Valine

Notes

Acknowledgments

We appreciate the financial support from the National Natural Science Foundation of China (NSFC project Nos. 20762017, 30821005 and 20776084), Program for Excellent Young Talents of Science and Technology of Guizhou Province (No.QKT200786), the National High Technology R&D Program (863 Program project # 2007AA021506) of the Ministry of Science and Technology of China (MOST), and the Shanghai Leading Academic Discipline Project (project nos. B203 and B505).

References

  1.  1.
     1. Hawksworth DL, Kirk PM, Sutton BC, Pegler DN (1995) Ainsworth and Bisby’s Dictionary of the Fungi, 8th edn. CABI, Wallingford, UK, pp 1–616Google Scholar
  2.  2.
     2. Hawksworth DL (2004) Fungal diversity and its implication for genetic resource collections. Stud Mycol 50:9–18Google Scholar
  3.  3.
     3. Hawksworth DL (2001) The magnitude of fungal diversity: the 1.5 million species estimate revisited. Mycol Res 105:1422–1432Google Scholar
  4. 4.
    Schmit JP, Mueller GM (2007) An estimate of the lower limit of global fungal diversity. Biodivers Conserv 16:99–111Google Scholar
  5. 5.
    Manoharachary C, Sridhar K, Singh R, Adholeya A, Suryanarayanan TS, Rawat S, Johri BN (2005) Fungal biodiversity: distribution, conservation and prospecting of fungi from India. Curr Sci 89:58–71Google Scholar
  6. 6.
    Hawksworth DL, Rossman AY (1997) Where are all the undescribed fungi? Phytopathology 87:888–891Google Scholar
  7. 7.
    Kirk PM, Cannon PF, David JC, Stalpers JA (2001) Ainsworth and Bisby’s Dictionary of the Fungi, 9th edn. CABI, Wallingford, UK, pp 1–655Google Scholar
  8. 8.
    Yang ZL, Zang M (2003) Tropical affinities of higher fungi in southern China. Acta Botanica Yunnanica 25:129–144Google Scholar
  9. 9.
    Stähelin HF (1996) The history of cyclosporin A (Sandimmune®) revisited: another point of view. Experientia 52:5–13Google Scholar
  10. 10.
    Wei J, Si SY, Chen XP, Wang L, Zhuang XL, Zou J, Chen HS, Cao LX, Feng H, Chen L (2006) Development and application of microbial natural products database. J Chin Antibiotics 31:119–121 (in Chinese)Google Scholar
  11. 11.
    Muegge I (2001) Heald SL and Brittelli D. Simple selection criteria for drug-like chemical matter. J Med Chem 44:1841–1846Google Scholar
  12. 12.
    Bérdy J (2005) Bioactive microbial metabolites: a personal view. J Antibiotics 58:1–26Google Scholar
  13. 13.
    Zhong J-J (ed.) (2004) Advances in biochemical engineering/biotechnology: biomanufacturing, vol 87. Springer-Verlag, HeidelbergGoogle Scholar
  14. 14.
    Strobel GA (2003) Endophytes as sources of bioactive products. Microbe Infect 5:535–544Google Scholar
  15. 15.
    König GM, Kehraus S, Seibert SF, Abdel-Lateff A, Müller D (2006) Natural products from marine organisms and their associated microbes. Chembiochem 7:229–238Google Scholar
  16. 16.
    Jiang W, Si SY, Chen XP,Wang L, Zhuang XL, Zou J, Chen HS, Cao LX, Feng H, Chen L (2006) Development and application of microbial natural products database. Chin J Antibiotics 31:119–121 (in Chinese)Google Scholar
  17. 17.
    Eicher T, Hauptmann S (2003) The chemistry of heterocycles: struture, reactions, syntheses and applications, 2nd edn. Wiley, Weinheim, pp 1–16Google Scholar
  18. 18.
    Liu JK (2005) N-Containing compounds of macromycetes. Chem Rev 105:2723–2742Google Scholar
  19. 19.
    Qin XD, Dong ZJ, Liu JK (2006) Two new compounds from the ascomycete Daldinia concentrica. Helv Chim Acta 89:450–455Google Scholar
  20. 20.
    Qin XD, Dong ZJ, Liu JK, Yang LM, Wang RR, Zheng YT, Lu Y, Wu YS, Zheng QT (2006) Concentricolide, an anti-HIV agent from the ascomycete Daldinia concentrica. Helv Chim Acta 89:127–133Google Scholar
  21. 21.
    Wang F, Liu JK (2004) A pair of novel heptentriol stereoisomers from the ascomycete Daldinia concentrica. Helv Chim Acta 87:2131–2134Google Scholar
  22. 22.
    Dong ZJ, Wang F, Wang RR, Yang LM, Zheng YT, Liu JK (2007) Chemical constituents of the fruiting bodies from the basidiomycete Suillus granulatus. Chin Tradit Herb Drugs 38:17–19 (in Chinese)Google Scholar
  23. 23.
    Wang YH, Tang JG, Wang RR, Yang LM, Dong ZJ, Du L, Shen X, Liu JK, Zheng YT (2007) Flazinamide, a novel b-carboline compound with anti-HIV actions. Biochem Biophys Res Commun 355:1091–1095Google Scholar
  24. 24.
    Kozlovsky AG, Zhelifonova VP, Antipova TV (2005) The fungus Penicillium citrinum, isolated from permafrost sediments, as a producer of ergot alkaloids and new quinoline alkaloids quinocitrinines. Appl Biochem Microbiol 41:499–502Google Scholar
  25. 25.
    Zhang Y, Li C, Swenson DC, Gloer JB, Wicklow DT, Dowd PF (2003) Novel antiinsectan oxalicine alkaloids from two undescribed fungicolous Penicillium spp. Org Lett 5:773–776Google Scholar
  26. 26.
    Smetanina OF, Kalinovsky AI, Khudyakova YV, Pivkin MV, Dmitrenok PS, Fedorov SN, Ji H, Kwak JY, Kuznetsova TA (2007) Indole alkaloids produced by a marine fungus isolate of Penicillium janthinellum Biourge. J Nat Prod 70:906–909Google Scholar
  27. 27.
    Xin ZH, Fang Y, Du L, Zhu T, Duan L, Chen J, Gu QQ, Zhu WM (2007) Aurantiomides A-C, quinazoline alkaloids from the sponge-derived fungus Penicillium aurantiogriseum SP0-19. J Nat Prod 70:853–855Google Scholar
  28. 28.
    Puri SC, Verma V, Amna T, Qazi GN, Spiteller M (2005) An endophytic fungus from Nothapodytes foetida that produces camptothecin. J Nat Prod 68:1717–1719Google Scholar
  29. 29.
    Kantola J, Kunnari T, Mäntsälä P, Ylihonkoa K (2003) Expanding the scope of aromatic polyketides by combinatorial biosynthesis. Comb Chem High Throughput Screen 6:501–512Google Scholar
  30. 30.
    Hopwood DA (2004) Cracking the polyketide code. PLOS Biol 2:166–169Google Scholar
  31. 31.
    Staunton J, Weissman KJ (2001) Polyketide biosynthesis: a millennium review. Nat Prod Rep 18:380–416Google Scholar
  32. 32.
    Mo SY, Yany YC, Shi JG (2003) Isolation and synthesis of phenigrins A and B. Acta Chim Sin 61:1161–1163 (in Chinese)Google Scholar
  33. 33.
    Mo SY, Wen YH, Yang YC, Shi JG (2003) Two benzyl dihydroflavones from Phellinus igniarius. Chin Chem Lett 14:810–813Google Scholar
  34. 34.
    Mo SY, Yang YC, He WY, Shi JG (2003) Two pyrone derivatives from fungus Phellinus Igniarius. Chin Chem Lett 14:704–706Google Scholar
  35. 35.
    Mo S, Wang S, Zhou G, Yang Y, Li Y, Chen X, Shi J (2004) Phelligridins C-F: cytotoxic pyrano[4,3-c][2]benzopyran-1,6-dione and furo[3,2-c]pyran-4-one derivatives from the fungus Phellinus igniarius. J Nat Prod 67:823–828Google Scholar
  36. 36.
    Wang Y, Mo SY, Wang SJ, Li S, Yang YC, Shi JG (2005) A unique highly oxygenated pyrano[4,3-c][2]benzopyran-1,6-dione derivative with antioxidant and cytotoxic activities from the fungus Phellinus igniarius. Org Lett 7:1675–1678Google Scholar
  37. 37.
    Wang Y, Shang XY, Wang SJ, Mo SY, Li S, Yang YC, Ye F, Shi JG, He L (2007) Structures, biogenesis, and biological activities of pyrano[4,3-c]isochromen-4-one derivatives from the fungus Phellinus igniarius. J Nat Prod 70:296–299Google Scholar
  38. 38.
    Wang Y, Wang SJ, Mo SY, Li S, Yang YC, Shi JG (2005) Phelligridimer A, a highly oxygenated and unsaturated 26-membered macrocyclic metabolite with antioxidant activity from the fungus Phellinus igniarius. Org Lett 7:4733–4736Google Scholar
  39. 39.
    Mao XL Economic fungi of China, 1st edn. Sciences Press, Beijing, 1998, pp 246Google Scholar
  40. 40.
    Wang F, Tan JW, Liu JK (2004) Vibratilicin: a novel compound from the Basidiomycete Cortinarius vibratilis. Helv Chim Acta 87:1912–1915Google Scholar
  41. 41.
    Hu L, Tan JW, Liu JK (2003) Chemical constituents of the basidiomycete Cortinarius umidicola. Z Naturforsch 58c:659–662Google Scholar
  42. 42.
    Quang DN, Harinantenaina L, Nishizawa T, Hashimoto T, Kohchi C, Soma GI, Asakawa Y (2006) Inhibitory activity of nitric oxide production in RAW 264.7 cells of daldinals A–C from the fungus Daldinia childiae and other metabolites isolated from inedible mushrooms. J Nat Med 60:303–307Google Scholar
  43. 43.
    Kang HS, Jun EM, Park SH, Heo SJ, Lee TS, Yoo ID, Kim JP (2007) Cyathusals A, B, and C, antioxidants from the fermented mushroom Cyathus stercoreus. J Nat Prod 70:1043–1045Google Scholar
  44. Lösgen S, Schlörke O, Meindl K, Herbst-Irmer R, Zeeck A (2007) Structure and biosynthesis of chaetocyclinones, new polyketides produced by an endosymbiotic fungus. Eur J Org Chem 2191–2196Google Scholar
  45. 45.
    Oh H, Swenson DC, Gloer JB (1998) Chaetochalasin A: a new bioactive metabolite from Chaetomium brasiliense. Tetrahedron Lett 39:7633–7636Google Scholar
  46. 46.
    Rether J, Erkel G, Anke T, Sterner O (2004) Oxaspirodion, a new inhibitor of inducible TNF-a expression from the ascomycete Chaetomium subspirale production, isolation and structure elucidation. J Antibiotics 57:493–495Google Scholar
  47. 47.
    Turbyville TJ, Wijeratne EMK, Liu MX, Burns AM, Seliga CJ, Luevano LA, David CL, Faeth SH, Whitesell L, Gunatilaka AAL (2006) Search for Hsp90 inhibitors with potential anticancer activity: isolation and SAR studies of radicicol and monocillin I from two plant-associated fungi of the sonoran desert. J Nat Prod 69:178–184Google Scholar
  48. 48.
    Ma J, Li Y, Ye Q, Li J, Hua Y, Ju D, Zhang D, Cooper R, Chang M (2000) Constituents of red yeast rice, a traditional food and medicine. J Agric Food Chem 48:5220–5225Google Scholar
  49. 49.
    Heber D, Yip I, Ashley JM, Elashoff DA, Elashoff RM, Go VL (1999) Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. Am J Clin Nutr 69:231–236Google Scholar
  50. 50.
    Juzlová P, Martínková L, Kren V (1996) Secondary metabolites of the fungus Monascus: a review. J Ind Microbiol Biotechnol 16:163–170Google Scholar
  51. 51.
    Wild D, Tóth G, Humpf HU (2002) New Monascus Metabolite Isolated from Red Yeast Rice (Angkak, Red Koji). J Agric Food Chem 50:3999–4002Google Scholar
  52. 52.
    Wild D, Tóth G, Humpf HU (2003) New Monascus metabolites with a pyridine structure in red fermented rice. J Agric Food Chem 51:5493–5496Google Scholar
  53. 53.
    Knecht A, Cramer B, Humpf HU (2006) New Monascus metabolites: structure elucidation and toxicological properties studied with immortalized human kidney epithelial cells. Mol Nutr Food Res 50:314–321Google Scholar
  54. 54.
    Thines E, Anke H, Sterner O (1998) Trichoflectin, a bioactive azaphilone from the Ascomycete Trichopezizella nidulus. J Nat Prod 61:306–308Google Scholar
  55. 55.
    Quang DN, Hashimoto T, Fournier J, Stadler M, Radulovic N, Asakawa Y (2005) Sassafrins A–D, new antimicrobial azaphilones from the fungus Creosphaeria sassafras. Tetrahedron 61:1743–1748Google Scholar
  56. 56.
    Wang XN, Tan RX, Liu JK (2005) Xylactam, a new nitrogen-containing compound from the fruiting bodies of ascomycete Xylaria euglossa. J Antibiotics 58:268–270Google Scholar
  57. 57.
    Holler U, Konig GM, Wright AD (1999) Three new metabolites from marine-derived fungi of the genera coniothyrium and microsphaeropsis. J Nat Prod 62:114–118Google Scholar
  58. 58.
    Oh H, Swenson DC, Gloer JB, Shearer CA (2001) Massarilactones A and B: novel secondary metabolites from the freshwater aquatic fungus Massarina tunicate. Tetrahedron Lett 42:975–977Google Scholar
  59. 59.
    Oh H, Swenson DC, Gloer JB, Shearer CA (2003) New bioactive rosigenin analogues and aromatic polyketide metabolites from the freshwater aquatic fungus Massarina tunicate. J Nat Prod 66:73–79Google Scholar
  60. 60.
    Li C, Nitka MV, Gloer JB (2003) Annularins A–H: new polyketide metabolites from the freshwater aquatic fungus Annulatascus triseptatus. J Nat Prod 66:1302–1306Google Scholar
  61. 61.
    Smith CJ, Abbanat D, Bernan VS, Maiese WM, Greenstein M, Jompa J, Tahir A, Ireland CM (2000) Novel polyketide metabolites from a species of marine fungi. J Nat Prod 63:142–145Google Scholar
  62. 62.
    Liu Z, Jensen PR, Fenical W (2003) A cyclic carbonate and related polyketides from a marine-derived fungus of the genus Phoma. Phytochemistry 64:571–574Google Scholar
  63. 63.
    Osterhage C, Schwibbe M, König GM, Wright AD (2000) Differences between marine and terrestrial Phoma species as determined by HPLC-DAD and HPLC-MS. Phytochem Anal 11:288–294Google Scholar
  64. 64.
    Kock I, Krohn K, Egold H, Draeger S, Schulz B, Rheinheimer J (2007) New massarilactones, Massarigenin E, and coniothyrenol, isolated from the endophytic fungus Coniothyrium sp. from Carpobrotus edulis. Eur J Org Chem 2186:2186–2190Google Scholar
  65. 65.
    Krohn K, Ullah Z, Hussain H, Fláorke U, Schulz B, Draeger S, Pescitelli G, Salvadori P, Antus S, Kurtán T (2007) Massarilactones E–G, new metabolites from the endophytic fungus Coniothyrium sp., associated with the plant Artimisia maritime. Chirality 19:464–470Google Scholar
  66. 66.
    Davis RA, Andjic V, Kotiw M, Shivas RG (2005) Phomoxins B and C: polyketides from an endophytic fungus of the genus Eupenicillium. Phytochemistry 66:2771–2775Google Scholar
  67. 67.
    Brady SF, Clardy J (2000) CR377, a new pentaketide antifungal agent isolated from an endophytic fungus. J Nat Prod 63:1447–1448Google Scholar
  68. 68.
    Jayasinghe L, Abbas HK, Jacob MR, Herath WHMW, Nanayakkara NPD (2006) N-Methyl-4-hydroxy-2-pyridinone analogues from Fusarium oxysporum. J Nat Prod 69:439–442Google Scholar
  69. 69.
    Wu X, Liu X, Jiang G, Lin Y, Chan W, Vrijmoed LLP (2005) Xyloketal G, a novel metabolite from the mangrove fungus Xylaria sp. 2508. Chem Nat Compd 41:27–29Google Scholar
  70. 70.
    Liu X, Xu F, Zhang Y, Liu L, Huang H, Cai X, Lin Y, Chan W (2006) Xyloketal H from the mangrove endophytic fungus Xylaria sp. 2508. Russ Chem Bull 55:1091–1092Google Scholar
  71. 71.
    Pettigrew JD, Bexrud JA, Freeman RP, Wilson PD (2004) Total synthesis of (±)-xyloketal D and model studies towards the total synthesis of (–)-xyloketal A. Heterocycles 62:445–452Google Scholar
  72. 72.
    Pettigrew JD, Wilson PD (2006) Synthesis of xyloketal A, B, C, D, and G analogues. J Org Chem 71:1620–1625Google Scholar
  73. 73.
    Qin XD, Liu JK (2004) Natural aromatic steroids as potential molecular fossils from the fruiting bodies of the ascomycete Daldinia concentrica. J Nat Prod 67:2133–2135Google Scholar
  74. 74.
    Wang F, Liu JK (2005) Two new steryl esters from the basidiomycete Tricholomopsis rutilans. Steroids 70:127–130Google Scholar
  75. 75.
    Zhang Y, Mill GL, Nair MG (2003) Cyclooxygenase inhibitory and antioxidant compounds from the fruiting body of an edible mushroom, Agrocybe aegerita. Phytomedicine 10:386–390Google Scholar
  76. 76.
    Gao JM, Zhang AL,Wang CY,Liu JK (2002) Constituents from the basidiomycetes Paxillus panuoides. Acta Botanica Boreali-Occidentalia Sin 22:391–395Google Scholar
  77. 77.
    Gao J, Hu L, Liu J (2001) A novel sterol from Chinese truffles Tuber indicum. Steroids 66:771–775Google Scholar
  78. 78.
    Wu SH, Luo XD, Ma YB, Liu JK, Wu DG, Zhao B, Lu Y, Zheng QT (2000) Two Novel Secoergosterols from the Fungus Tylopilus plumbeoviolaceus. J Nat Prod 63:534–536Google Scholar
  79. 79.
    Barrero AF, Oltra JE, Poyatos JA, Jiménez D, Oliver E (1998) Phycomysterols and other sterols from the fungus Phycomyces blakesleeanus. J Nat Prod 61:1491–1496Google Scholar
  80. 80.
    Lu H, Zou WX, Meng JC, Hu J, Tan RX (2000) New bioactive metabolites produced by Colletotrichum sp., an endophytic fungus in Artemisia annua. Plant Sci 151:67–73Google Scholar
  81. 81.
    Bok JW, Lermer L, Chilton J, Klingeman HG, Towers GH (1999) Antitumor sterols from the mycelia of Cordyceps sinensis. Phytochemistry 51:891–898Google Scholar
  82. 82.
    Nam KS, Jo YS, Kim YH, Hyun JW, Kim HW (2001) Cytotoxic activities of acetoxyscirpenediol and ergosterol peroxide from Paecilomyces tenuipes. Life Sci 69:229–237Google Scholar
  83. 83.
    Oh GS, Hong KH, Oh H, Pae HO, Kim IK, Kim NY, Kwon TO, Shin MK, Chung HT (2001) 4-Acetyl-12,13-epoxyl-9-trichothecene-3,15-diol isolated from the fruiting bodies of Isaria japonica YASUDA induces apoptosis of human leukemia cells (HL-60). Biol Pharm Bull 24:785–789Google Scholar
  84. 84.
    Stierle A, Strobel G, Stierle D (1993) Taxol and taxane production by Taxomyces andreanae, an endophytic fungus of Pacific yew. Science 260:214–216Google Scholar
  85. 85.
    Strobel G, Yang X, Sears J, Kramer R, Sidhu RS, Hess WM (1996) Taxol from Pestalotiopsis microspora, an endophytic fungus of Taxus wallachiana. Microbiology 142:435–440Google Scholar
  86. 86.
    Shrestha K, Strobel GA, Shrivastava SP, Gewali M (2001) Evidence for paclitaxel from three new endophytic fungi of Himalayan yew of Nepal. Planta Med 67:374–376Google Scholar
  87. 87.
    Wang J, Li G, Lu H, Zheng Z, Huang Y, Su W (2000) Taxol from Tubercularia sp. strain TF5, an endophytic fungus of Taxus mairei. FEMS Microbiol Lett 193:249–253Google Scholar
  88. 88.
    Zhou DP, Ping WX, Sun JQ, Zhou XH, Liu XL, Yang DZ, Zhang JP, Zheng XQ (2001) Isolation of taxol producing fungi. J Microbiol 21:18–20 (in Chinese)Google Scholar
  89. 89.
    Zhou DP, Sun JQ, Yu HY, Ping WX, Zheng XQ (2001) Nodulisporium,a genus new to China. Mycosystema 20:277–278Google Scholar
  90. 90.
    Li JY, Strobel G, Sidhu R, Hess WM, Ford EJ (1996) Endophytic taxol-producing fungi from bald cypress, Taxodium distichum. Microbiology 142:2223–2226Google Scholar
  91. 91.
    Strobel GA, Ford E, Li JY, Sears J, Sidhu RS, Hess WM (1999) Seimatoantlerium tepuiense gen. nov., a unique epiphytic fungus producing taxol from the Venezuelan Guyana. Syst Appl Microbiol 22:426–433Google Scholar
  92. 92.
    Strobel G, Daisy B (2003) Bioprospecting for microbial endophytes and their natural products. Microbiol Mol Biol Rev 67:491–502Google Scholar
  93. 93.
    Shibata H, Tokunaga T, Karaswa D, Hirota A, Nakayama M, Nozaki H, Tada T (1989) Isolation and characterization of new bitter diterpenoids from the fungus Sarcodon scabrosus. Agric Biol Chem 53:3373–3375Google Scholar
  94. 94.
    Ohta T, Kita T, Kobayashi N, Obara Y, Nakahata N, Ohizumi Y, Takaya Y, Oshima Y (1998) Scabronine A, a novel diterpenoid having potent inductive activity of the nerve growth factor synthesis, isolated from the mushroom, Sarcodon scabrosus. Tetrahedron Lett 39:6229–6232Google Scholar
  95. 95.
    Kita T, Takaya Y, Oshima Y (1998) Scabronines B, C, D, E and F, novel diterpenoids showing stimulating activity of nerve growth factor-synthesis, from the mushroom Sarcodon scabrosus. Tetrahedron 54:11877–11886Google Scholar
  96. 96.
    Ma BJ, Zhu HJ, Liu JK (2004) Isolation and characterization of new bitter diterpenoids from the basidiomycete Sarcodon scabrosus. Helv Chim Acta 87:2877–2881Google Scholar
  97. 97.
    Ma BJ, Liu JK (2005) A new bitter diterpenoid from Sarcodon scabrosus. J Basic Microbiol 45:328–330Google Scholar
  98. 98.
    Bills GF, Polishook JD, Goetz MA, Sullivan RF, Jr JFW (2002) Chaunopycnis pustulata sp. nov., a new clavicipitalean anamorph producing metabolites that modulate potassium ion channels. Mycol Prog 1:3–17Google Scholar
  99.  99.
     99. Tang W, Gu T, Zhong JJ (2006) Separation of targeted ganoderic acids from Ganoderma lucidum by reversed phase liquid chromatography with ultraviolet and mass spectrometry detections. Biochem Eng J 32:205–210Google Scholar
  100. 100.
    Tang W, Liu JW, Zhao WM, Wei DZ, Zhong JJ (2006) Ganoderic acid T from Ganoderma lucidum mycelia induces mitochondria mediated apoptosis in lung cancer cells. Life Sci 80:205–211Google Scholar
  101. 101.
    Wu TS, Shi LS, Kuo SC (2001) Cytotoxicity of Ganoderma lucidum triterpenes. J Nat Prod 64:1121–1122Google Scholar
  102. 102.
    Gao JJ, Min BS, Ahn EM, Nakamura N, Lee HK, Hattori M (2002) New triterpene aldehydes, lucialdehydes A–C, from Ganoderma lucidum and their cytotoxicity against murine and human tumor cells. Chem Pharm Bull 50:837–840Google Scholar
  103. 103.
    Akihisa T, Nakamura Y, Tokuda H, Uchiyama E, Suzuki T, Kimura Y, Uchikura K, Nishino H (2007) Triterpene acids from Poria cocos and their anti-tumor-promoting effects. J Nat Prod 70:948–953Google Scholar
  104. 104.
    Quang DN, Hashimoto T, Tanaka M, Takaoka S, Asakawa Y (2004) Tyromycic acids B–E, new lanostane triterpenoids from the mushroom Tyromyces fissilis. J Nat Prod 67:148–151Google Scholar
  105. 105.
    Quang DN, Hashimoto T, Tanaka M, Asakawa Y (2003) Tyromycic acids F and G: two new triterpenoids from the mushroom Tyromyces fissilis. Chem Pharm Bull 51:1441–1443Google Scholar
  106. 106.
    Shao HJ, Qing C, Wang F, Zhang YL, Luo DQ, Liu JK (2005) A new cytotoxic lanostane triterpenoid from the basidiomycete Hebeloma versipelle. J Antibiotics 58:828–831Google Scholar
  107. 107.
    Clericuzio M, Mella M, Vita-Finzi P, Zema M, Vidari G (2004) Cucurbitane triterpenoids from Leucopaxillus gentianeus. J Nat Prod 67:1823–1828Google Scholar
  108. 108.
    Clericuzio M, Tabasso S, Bianco MA, Pratesi G, Beretta G, Tinelli S, Zunino F, Vidari G (2006) Cucurbitane triterpenes from the fruiting bodies and cultivated mycelia of Leucopaxillus gentianeus. J Nat Prod 69:1796–1799Google Scholar
  109. 109.
    Hashimoto T, Asakawa Y (1998) Biologically active substances of Japanese inedible mushrooms. Heterocycles 47:1110–1121Google Scholar
  110. 110.
    Stadler M, Baumgartner M, Grothe T, Mühlbauer A, Seip S, Wollweber H (2001) Concentricol, a taxonomically significant triterpenoid from Daldinia concentrica. Phytochemistry 56:787–793Google Scholar
  111. 111.
    Quang DN, Hashimoto T, Tanaka M, Baumgartnerc M, Stadler M, Asakawa Y (2002) Concentriols B, C and D, three squalene-type triterpenoids from the ascomycete Daldinia concentrica. Phytochemistry 61:345–353Google Scholar
  112. 112.
    Stadler M, Wollweber H, Mühlbauer A, Henkel T, Asakawa Y, Hashimoto T, Rogers JD, Ju YM, Wetzstein HG, Tichy HV (2001) Secondary metabolite profiles, genetic fingerprints and taxonomy of Daldinia and allies. Mycotaxon 77:379–429Google Scholar
  113. 113.
    Deyrup ST, Gloer JB, O’Donnell K, Wicklow DT (2007) Kolokosides A–D: triterpenoid glycosides from a Hawaiian isolate of Xylaria sp. J Nat Prod 70:378–382Google Scholar
  114. 114.
    Tan JW, Dong ZJ, Liu JK (2000) New terpenoids from basidiomycetes Russula lepida. Helv Chim Acta 83:3191–3197Google Scholar
  115. 115.
    Tan JW, Dong ZJ, Liu JK (2001) A new sesquiterpenoid from Russula lepida. Acta Botanica Sin 43:329–330 (in Chinese)Google Scholar
  116. 116.
    Tan J, Dong Z, Hu L, Liu J (2003) Lepidamine, the first aristolane-type sesquiterpene alkaloid from the basidiomycete Russula lepida. Helv Chim Acta 86:307–309Google Scholar
  117. 117.
    Tan JW, Dong ZJ, Ding ZH, Liu JK (2002) Lepidolide, a novel seco-ring-A cucurbitane triterpenoid from Russula lepida (basidiomycetes). Z Naturforsch 57c:963–965Google Scholar
  118. 118.
    Gao JM, Dong ZJ, Liu JK (2001) A new ceramide from the basidiomycete Russula cyanoxantha. Lipids 36:175–180Google Scholar
  119. 119.
    Tan JW, Xu JB, Dong ZJ, Luo DQ, Liu JK (2004) Nigricanin, the first ellagic acid derived metabolite from the basidiomycete Russula nigricans. Helv Chim Acta 87:1025–1028Google Scholar
  120. 120.
    Luo DQ, Wang F, Bian XY, Liu JK (2005) Rufuslactone, a new antifungal sesquiterpene from the fruiting bodies of the basidiomycete Lactarius rufus. J Antibiotics 58:456–459Google Scholar
  121. 121.
    Hu L, Liu JK (2002) The first humulene type sesquiterpene from Lactarius hirtipes. Z Naturforsch 57c:571–574Google Scholar
  122. 122.
    Luo DQ, Gao Y, Gao JM, Wang F, Yang XL, Liu JK (2006) Humulane-type sesquiterpenoids from the mushroom Lactarius mitissimus. J Nat Prod 69:1354–1357Google Scholar
  123. 123.
    Luo DQ, Shao HJ, Zhu HJ, Liu JK (2005) Activity in vitro and in vivo against plant pathogenic fungi of grifolin isolated from the basidiomycete Albatrellus dispansus. Z Naturforsch 60c:50–56Google Scholar
  124. 124.
    Ye M, Liu JK, Lu ZX, Zhao Y, Liu SF, Li LL, Tan M,Weng XX, Li W, Cao Y (2005) Grifolin, a potential antitumor natural product from the mushroom Albatrellus confluens, inhibits tumor cell growth by inducing apoptosis in vitro. FEBS Lett 579:3437–3443Google Scholar
  125. 125.
    Nukata M, Hashimoto T, Yamamoto I, Iwasaki N, Tanaka M, Asakawa Y (2002) Neogrifolin derivatives possessing anti-oxidative activity from the mushroom Albatrellus ovinus. Phytochemistry 59:731–737Google Scholar
  126. 126.
    Quang DN, Hashimoto T, Arakawa Y, Kohchi C, Nishizawa T, Soma G, Asakawa Y (2006) Grifolin derivatives from Albatrellus caeruleoporus, new inhibitors of nitric oxide production in RAW 264.7 cells. Bioorg Med Chem. 14:164–168Google Scholar
  127. 127.
    Ding ZH, Dong ZJ, Liu JK (2001) Albaconol, A novel prenylated resorcinol (benzene-1,3-diol) from basidiomycetes Albatrellus confluens. Helv Chim Acta 84:259–262Google Scholar
  128. 128.
    Liu MH, Qing C, Liu JK, Zhang YL, Wang L, Ji SY (2004) Study on the antitumor activity of albaconol and its effect on DNA topoisomerase II. Chin Pharmacol Bull 20:1224–1228 (in Chinese)Google Scholar
  129. 129.
    Smetanina OF, Kuznetsova TA, Gerasimenko AV, Kalinovsky AI, Pivkin MV, Dmitrenok PC, Elyakov GB (2004) Metabolites of the marine fungus Humicola fuscoatra KMM 4629. Russ Chem Bull 53:2643–2646Google Scholar
  130. 130.
    Oh H, Gloer JB, Shearer CA (1999) Massarinolins A-C: new bioactive sesquiterpenoids from the aquatic fungus Massarina tunicate. J Nat Prod 62:497–501.Google Scholar
  131. 131.
    Xiao JH, Zhong JJ (2007) Secondary metabolites from Cordyceps species and their antitumor activity studies. Recent Patents Biotechnol 1:123–137Google Scholar
  132. 132.
    Jow GM, Chou CJ, Chen BF, Tsai JH (2004) Beauvericin induces cytotoxic effects in human acute lymphoblastic leukemia cells through cytochrome c release, caspase 3 activation: the causative role of calcium. Cancer Lett 216:165–173Google Scholar
  133. 133.
    Nilanonta C, Isaka M, Kittakoop P, Trakulnaleamsai S, Tanticharoen M, Thebtaranonth Y (2002) Precursor-directed biosynthesis of beauvericin analogs by the insect pathogenic fungus Paecilomyces tenuipes BBC 1614. Tetrahedron 58:3355–3360Google Scholar
  134. 134.
    Wu SN, Chen H, Liu YC, Chiang HT (2002) Block of L-type Ca2+ current by bauvericin, a toxic cyclopeptide, in the NG108-15 neuronal cell line. Chem Res Toxicol 15:854–860Google Scholar
  135. 135.
    Jia JM, Ma XC, Wu CF, Wu LJ, Hu GS (2005) Cordycedipeptide A, a new cyclodipeptide from the culture liquid. Chem Pharm Bull 53:582–583Google Scholar
  136. 136.
    Rukachaisirikul V, Chantaruk S, Tansakul C, et al (2006) A cyclopeptide from the insect pathogenic fungus Cordyceps sp. BCC 1788. J Nat Prod 69:305–307Google Scholar
  137. 137.
    Krasnoff SB, Reátegui RF, Wagenaar MM, Gloer JB, Gibson DM (2005) Cicadapeptins I and II: new aib-containing peptides from the entomopathogenic fungus Cordyceps heteropoda. J Nat Prod 68:50–55Google Scholar
  138. 138.
    Ravindra G, Ranganayaki RS, Raghothama S, Srinivasan MC, Gilardi RD, Karle IL, Balaram P (2004) Two novel hexadepsipeptides with several modified amino acid residues isolated from the fungus Isaria. Chem Biodivers 1:489–504Google Scholar
  139. 139.
    Sabareesh V, Ranganayaki RS, Raghothama S, Bopanna MP, Balaram H, Srinivasan MC, Balaram P (2007) Identification and characterization of a library of microheterogeneous cyclohexadepsipeptides from the fungus Isaria. J Nat Prod 70:715–729Google Scholar
  140. 140.
    Degenkolb T, Berg A, Gams W, Schlegel B, Gräfe U (2003) The occurrence of peptaibols and structurally related peptaibiotics in fungi and their mass spectrometric identification via diagnostic fragment ions. J Pept Sci 9:666–678Google Scholar
  141. 141.
    Chugh JK, Wallace BA (2001) Peptaibols: models for ion channels. Biochem Soc Trans 29:565–570Google Scholar
  142. 142.
    Summers MY, Kong F, Feng X, Siegel MM, Janso JE, Graziani EI, Carter GT (2007) Septocylindrins A and B: peptaibols produced by the terrestrial fungus Septocylindrium sp. LL-Z1518. J Nat Prod 70:391–396Google Scholar
  143. 143.
    Xie ST, Song XY, Shi M, Chen XL, Sun CY, Zhang YZ (2006) Antimicrobial activities of trichokonins: peptaibols-like antimicrobial peptides produced by Trichoderma koningii SMF2. J Shandong Univ 41(6):140–144 (in Chinese)Google Scholar
  144. 144.
    Liu JK (2006) Natural terphenyls: developments since 1877. Chem Rev 106:2209–2223Google Scholar
  145. 145.
    Quang DN, Hashimoto T, Asakawai Y (2006) Inedible mushrooms: a good source of biologically active substances. Chem Rec 6:79–99Google Scholar
  146. 146.
    Hu L, Liu JK (2001) Two novel phenylacetoxylated p-terphenyls from Thelephora ganbajun. Zang Z Naturforsch 56c:983–987Google Scholar
  147. 147.
    Hu L, Gao JM, Liu JK (2001) Unusual poly(phenylacetyloxy)-substituted 1,1′:4′,1″-terphenyl derivatives from fruiting bodies of the basidiomycete Thelephora ganbajun. Helv Chim Acta 84:3342–3349Google Scholar
  148. 148.
    Yun BS, Lee IK, Kim JP, Yoo ID (2000) Curtisians A and D, new free radical scavengers from the mushroom Paxillus curtisii. J Antibiotics 53:114–122Google Scholar
  149. 149.
    Quang DN, Hashimoto T, Nukada M, Yamamoto I, Tanaka M, Asakawa Y (2003) Curtisians E–H: four p-terphenyl derivatives from the inedible mushroom Paxillus curtisii. Phytochemistry 64:649–654Google Scholar
  150. 150.
    Quang DN, Hashimoto T, Nukada M, Yamamoto I, Tanaka M, Asakawa Y (2003) Antioxidant activity of custisians I–L from the inedible mushroom Paxillus curtisii. Planta Medica 69:1063–1066Google Scholar
  151. 151.
    Quang DN, Hashimoto T, Nukada M, Yamamoto I, Tanaka M, Asakawa Y (2003) Curtisians M—Q: five novel p-terphenyl derivatives from the mushroom. Paxillus curtisii Chem Pharm Bull 51:1064–1067Google Scholar
  152. 152.
    Ma BJ, Hu Q, Liu JK (2006) A new p-terphenyl derivative from fruiting bodies of the basidiomycete Sarcodon laevigatum. J Basic Microbiol 46:239–242Google Scholar
  153. 153.
    Gao JM, Zhang AL, Zhang CL, Liu JK (2004) Paxillamide: a novel phytosphingosine derivative from the fruiting bodies of Paxillus panuoides. Helv Chim Acta 87:1483–1487Google Scholar
  154. 154.
    Gao JM, Zhang AL, Wang CY, Wang XH, Liu JK (2002) A new ceramide from the Ascomycete Tuber indicum. Chin Chem Lett 13:325–326Google Scholar
  155. 155.
    Gao JM, Zhang AL, Chen H, Liu JK (2004) Molecular species of ceramides from the ascomycete Tuber indicum. Chem Phys Lipids 131:205–213Google Scholar
  156. 156.
    Gao JM, Wang CY, Zhang AL, Liu JK (2001) A new trihydroxy fatty acid from the ascomycete, Chinese truffle Tuber indicum. Lipids 36:1365–1370Google Scholar
  157. 157.
    Nicholas GM, Blunt JW, Munro MHG (2001) Cortamidine oxide, a novel disulfide metabolite from the New Zealand basidiomycete (mushroom) Cortinarius species. J Nat Prod 64:341–344Google Scholar
  158. 158.
    Wang F, Luo DQ, Liu JK (2005) Aurovertin E, a new polyene pyrone from the basidiomycete Albatrellus confluens. J Antibiotics 58:412–415Google Scholar
  159. 159.
    Qin XD, Liu JK (2004) Three new homologous 3-alkyl-1,4-benzoquinones from the fruiting bodies of Daldinia concentrica. Helv Chim Acta 87:2022–2024Google Scholar
  160. 160.
    Eyberger AL, Dondapati R, Porter JR (2006) Endophyte fungal isolates from Podophyllum peltatum produce Podophyllotoxin. J Nat Prod 69:1121–1124Google Scholar
  161. 161.
    Puri SC, Nazir A, Chawla R, Arora R, Riyaz-ul-Hasan S, Amna T, Ahmed B, Verma V, Singh S, Sagar R, Sharma A, Kumar R, Sharma RK, Qazi GN (2006) The endophytic fungus Trametes hirsuta as a novel alternative source of podophyllotoxin and related aryl tetralin lignans. J Biotechnol 122:494–510Google Scholar
  162. 162.
    Soman AG, Gloer JB, Koster B, Malloch D (1999) Sporovexins A–C and a new preussomerin analog: antibacterial and antifungal metabolites from the Coprophilous fungus Sporormiella vexans. J Nat Prod 62:659–661Google Scholar
  163. 163.
    Chadwick DJ, Whelan J (eds) (1992) Secondary metabolites: their function and evolution. Ciba Foundation Symposium 171. Wiley, Chichester, UK, pp 1–328Google Scholar
  164. 164.
    Demain AL (2006) From natural products discovery to commercialization: a success story. J Ind Microbiol Biotechnol 33:486–495Google Scholar
  165. 165.
    Zjawiony JK (2004) Biologically active compounds from aphyllophorales (Polypore) fungi. J Nat Prod 67:300–310Google Scholar
  166. 166.
    Song XY, Shen QT, Xie ST, Chen XL, Sun CY, Zhang YZ (2006) Broad-spectrum antimicrobial activityand high stability of trichokonins from Trichoderma koningii SMF2 against plant pathogens. FEMS Microbiol Lett 260:119–125Google Scholar
  167. 167.
    Vicente MF, Basilio A, Cabello A, Peláez F (2003) Microbial natural products as a source of antifungals. Clin Microbiol Infect 9:15–32Google Scholar
  168. 168.
    Neamati N (2001) Structure-based HIV-1 integrase-inhibitor design: a future perspective. Exp Opin Invest Drugs 10:281–296Google Scholar
  169. 169.
    Singh SB, Jayasuriy H, Dewey R, Polishook JD, Dombrowski AW, Zink DL, Guan Z, Collado J, Platas G, Pelaez F, Felock P, Hazuda DJ (2003) Isolation, structure, and HIV-1-integrase inhibitory activity of structurally diverse fungal metabolites. J Ind Microbiol Biotechnol 30:721–731Google Scholar
  170. 170.
    Kim KM, Kwon YG, Chung HT, Yun YG, Pae HO, Han JA, Ha KS, Kim TW, Kim YM (2003) Methanol extract of Cordyceps pruinosa inhibits in vitro and in vivo inflammatory mediators by suppressing NF-kappa B activation. Toxicol Appl Pharm 190:1–8Google Scholar
  171. 171.
    Lipsky LP, Abramson SB, Crofford L, Dubois RN, Simon LS, Van de Putte LB (1998) The classification of cyclooxygenases inhibitors. J Rheumatol 25:2298–2303Google Scholar
  172. 172.
    Smith CJ, Zhang Y, Koboldt CM, Muhammad J, Zweifel BS, Shaffer A, Talley JJ, Masferrer JL, Seibert K, Isakson PC (1998) Pharmacological analysis of cyclooxygenase-1 in inflammation. Proc Natl Acad Sci U S A 95:13313–13318Google Scholar
  173. 173.
    Sun B, Fukuhara M (1997) Effects of co-administration of butylated hydroxytoluene, butylated hydroxyanisole and flavonoids on the activation of mutagens and drug-metabolizing enzymes in mice. Toxicology 122:61–72Google Scholar
  174. 174.
    Yen GC, Wu JY (1999) Antioxidant and radical scavenging properties of extracts from Ganoderma tsugae. Food Chem 65:375–379Google Scholar
  175. 175.
    Sun J, He H, Xie BJ (2004) Novel antioxidant peptides from fermented mushroom Ganoderma lucidum. J Agric Food Chem 52:6646–6652Google Scholar
  176. 176.
    Fang LZ, Qing C, Shao HJ, Yang YD, Dong ZJ, Wang F, Zhao W, Yang WQ, Liu JK (2006) Hypocrellin D, a cytotoxic fungal pigment from fruiting bodies of the ascomycete Shiraia bambusicola. J Antibiot 59:351–354Google Scholar
  177. 177.
    Whitesell L, Lindquist SL (2005) Hsp90 and the chaperoning of cancer. Nat Rev Cancer 5:761–772Google Scholar
  178. 178.
    Chen Y, Ding J (2004) Heat shock protein 90: novel target for cancer therapy. Chin J Cancer 23:968–974 (in Chinese)Google Scholar
  179. 179.
    Demain AL (1999) Pharmaceutically active secondary metabolites of microorganisms. Appl Microbiol Biotechnol 52:455–463Google Scholar
  180. 180.
    Fenteany G, Zhu S (2003) Small-molecule inhibitors of actin dynamics and cell motility. Curr Top Med Chem 3:593–616Google Scholar
  181. 181.
    Carmeliet P (2003) Angiogenesis in health and disease. Nat Med 9:653–660Google Scholar
  182. 182.
    Zhan J, Burns AM, Liu MX, Faeth SH, Gunatilaka AAL (2007) Search for cell motility and angiogenesis inhibitors with potential anticancer activity: beauvericin and other constituents of two endophytic strains of Fusarium oxysporum. J Nat Prod 70:227–232Google Scholar
  183. 183.
    Hosoe T, Iizuka T, Komai SI, Wakana D, Itabashi T, Nozawa K, Fukushima K, Kawai KI (2005) 4-Benzyl-3-phenyl-5H-furan-2-one, a vasodilator isolated from Malbranchea filamentosa IFM 41300. Phytochemistry 66:2776–2779Google Scholar
  184. 184.
    Liu DZ, Wang F, Liao TG, Tang JG, Steglich W, Zhu HJ, Liu JK (2006) Vibralactone: a lipase inhibitor with an unusual fused β-lactone produced by cultures of the basidiomycete Boreostereum vibrans. Org Lett 8:5749–5752Google Scholar
  185. 185.
    Sim KL, Perry D (1997) Analysis of swainsonine and its early metabolic precursors in cultures of Metarhizium anisopliae. Glycoconjugate J 14:661–668Google Scholar
  186. Skrobek A, Shah FA, Butt TM (2008) Destruxin production by the entomogenous fungus Metarhizium anisopliae in insects and factors influencing their degradation. Biocontrol 53:361–373Google Scholar
  187. 187.
    Asaff A, Cerda-García-Rojas C, Torre M de la (2005) Isolation of dipicolinic acid as an insecticidal toxin from Paecilomyces fumosoroseus. Appl Microbiol Biotechnol 68:542–547Google Scholar
  188. 188.
    Salituro GM, Pelaez F, Zhang BB (2001) Discovery of a small molecule insulin receptor activator.Recent Prog Horm Res 56:107–126Google Scholar
  189. 189.
    Wagner R, Mitchell DA, Sassaki GL, de Almeida Amazonas MAL, Berovic M (2003) Current techniques for the cultivation of Ganoderma lucidum for the production of biomass, ganoderic acid and polysaccharides. Food Technol Biotechnol 41:371–382Google Scholar
  190. 190.
    Zhong JJ, Tang YJ (2004) Submerged cultivation of medicinal mushrooms for production of valuable bioactive metabolites. Adv Biochem Eng Biotechnol 87:25–59Google Scholar
  191. 191.
    Tang YJ, Zhu LW, Li HM, Li DS (2007) Submerged culture of mushrooms in bioreactors – challenges, current state-of-the-art, and future prospects. Food Technol Biotechnol 45:221–229Google Scholar
  192. 192.
    Tang YJ, Zhu LL, Li DS, Mi ZY, Li HM (2008) Significance of inoculation density and carbon source on the mycelial growth and tuber polysaccharides production by submerged fermentation of Chinese truffle Tuber sinense. Process Biochem 43:576–586Google Scholar
  193. 193.
    Liu RS, Li DS, Li HM, Tang YJ (2008) Response surface modeling the significance of nitrogen source on the cell growth and tuber polysaccharides production by submerged cultivation of Chinese truffle Tuber sinense. Process Biochem 43:868–876Google Scholar
  194. 194.
    Tang YJ, Zhu LL, Liu RS, Li HM, Li DS, Mi ZY (2008) Quantitative response of cell growth and tuber polysaccharides biosynthesis by medicinal mushroom Chinese truffle Tuber sinense to metal ion in culture medium. Bioresour Technol 99:7606–7615Google Scholar
  195. 195.
    Wang G, Li YY, Li DS, Tang YJ (2008) Determination of 5α-androst-16-en-3α-ol in truffle fermentation broth by solid-phase extraction coupled with gas chromatography-flame ionization detector/electron impact mass spectrometry. J Chromatogr B 870:209–215Google Scholar
  196. 196.
    Wang G, Zhao J, Liu JW, Huang YP, Tang W, Zhong JJ (2007) Enhancement of IL-2 and IFN-γ expression and NK cells activity involved in the anti-tumor effect of ganoderic acid Me in vivo. Int Immunopharmacol 7:864–870Google Scholar
  197. 197.
    Chen NH, Liu JW, Zhong JJ (2008) Ganoderic acid Me inhibits tumor invasion through down-regulating matrix metalloproteinases 2/9 gene expression. J Pharmacol Sci 108:212–216Google Scholar
  198. 198.
    El-Mekkawy S, Meselhy MR, Nakamura N, Tezuka Y, Hattori M, Kakiuchi N, Shimotohno K, Kawahata T, Otake T (1998) Anti-HIV-1 and anti-HIV-1-protease substances from Ganoderma lucidum. Phytochemistry 49:1651–1657Google Scholar
  199. 199.
    Fang QH, Zhong JJ (2002) Effect of initial pH on production of ganoderic acid and polysaccharide by submerged fermentation of Ganoderma lucidum. Process Biochem 37:769–774Google Scholar
  200. 200.
    Tang YJ, Zhong JJ (2003) Role of oxygen supply in submerged fermentation of Ganoderma lucidum for production of Ganoderma polysaccharide and ganoderic acid. Enzyme Microb Technol 32:478–484Google Scholar
  201. 201.
    Fang QH, Zhong JJ (2002) Two-stage culture process for improved production of gano­deric acid by liquid fermentation of higher fungus Ganoderma lucidum. Biotechnol Prog 18:51–54Google Scholar
  202. 202.
    Tang YJ, Zhong JJ (2002) Fed-batch fermentation of Ganoderma lucidum for hyperproduction of polysaccharide and ganoderic acid. Enzyme Microb Technol 31:20–28Google Scholar
  203. 203.
    Tang YJ, Zhong JJ (2003) Scale-up of a liquid static culture process for hyperproduction of ganoderic acid by the medicinal mushroom Ganoderma lucidum. Biotechnol Prog 19:1842–1846Google Scholar
  204. 204.
    Mao XB, Zhong JJ (2004) Hyperproduction of cordycepin by two-stage dissolved oxygen control in submerged cultivation of medicinal mushroom Cordyceps militaris in bioreactors. Biotechnol Prog 20:1408–1413Google Scholar
  205. 205.
    Li Y, Dong XY, Sun Y (2005) High-speed chromatographic purification of plasmid DNA with a customized porous hydrophobic adsorbent. Biochem Eng J 27:33–39Google Scholar
  206. 206.
    Harsa S, Furusaki S (2001) Chromatographic separation of amyloglucosidase from the mixtures of enzymes. Biochem Eng J 8:257–261Google Scholar
  207. 207.
    Schwarz M, Hillebrand S, Habben S, Degenhardt A, Winterhalter P (2003) Application of high-speed countercurrent chromatography to the large-scale isolation of anthocyanins. Biochem Eng J 14:179–189Google Scholar
  208. 208.
    Kikuchi T, Kanomi S, Kadota S, Murai Y, Tsubono K, Ogita Z (1986) Constituents of the fungus Ganoderma lucidum (F.R.) Karst. 1. Structures of ganoderic acid-C2, acid-E, acid-I, AND acid-K, lucidenic acid-F AND related-compounds. Chem Pharm Bull 34:3695–3712Google Scholar
  209. 209.
    Lin L, Shiao S (1987) Separation of oxygenated triterpenoids from Ganoderma lucidum by high performance liquid chromatography. J Chromatogr A 410:195–200Google Scholar
  210. 210.
    Shiao M, Lin L, Chen C (1989) Determination of stereo and positional isomers of oxygenated triterpenoids by reversed phase high performance liquid chromatography. J Lipid Res 30:287–291Google Scholar
  211. 211.
    Mutlib A, Strupczewski J, Chesson S (1995) Application of. hyphenated LC/NMR and LC/MS techniques in rapid identification in vitro and in vivo metabolites of iloperidone. Drug Metab Dispos 23:951–964Google Scholar
  212. 212.
    Mutlib A, Klein J (1998) Application of liquid chromatography/mass spectrometry in accelerating the identification of human liver cytochrome P450 isoforms involved in the metabolism of iloperidone. J Pharmacol Exp Ther 286:1285–1293Google Scholar

Copyright information

© Springer-Verlag London 2009

Authors and Affiliations

  1. 1.School of Life Sciences and Biotechnology, Key Laboratory of Microbial Metabolism Ministry of EducationShanghai Jiao Tong UniversityShanghaiChina
  2. 2.Key Laboratory of Cell Engineering of Guizhou ProvinceAffiliated Hospital of Zunyi Medical CollegeZunyiChina
  3. 3.State Key Laboratory of Bioreactor EngineeringEast China University of Science and TechnologyShanghaiChina

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