Biosynthesis of Fungal Polyketides

Part of the The Mycota book series (MYCOTA, volume 15)


Fungal polyketides comprise of a large group of structurally diverse compounds with a wide range of biological activities. These compounds are biosynthesised by Type I iterative polyketide synthases (PKS) which can be further defined as non-reducing (nr), partially reducing (pr) and highly reducing (hr) PKS. However, knowledge of the type of PKS is insufficient to predict the actual structure of the final compound. Advances in genome sequencing and bioinformatics technologies, coupled with increased understanding of fungal polyketide tailoring enzymes, make higher-order predictions about the structural family possible. Due to the increased understanding of fungal polyketide biosynthesis and the increased number of pathways characterised, engineering these pathways for the production of novel compounds is becoming more common. This review covers the recent progress in understanding the biosynthesis and engineering of fungal polyketides.


Polyketide Synthase (PKS) Resorcylic Acid Lactones (RAL) Squalestatin Monascus Biosynthetic Gene Cluster (BGC) 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Abramson D, Usleber E, Märtlbauer E (2001) Immunochemical method for citrinin. In: Mycotoxin protocols, vol 157. Humana, Totowa, NJ, pp 195–204CrossRefGoogle Scholar
  2. Ahuja M, Chiang Y-M, Chang S-L et al (2012) Illuminating the diversity of aromatic polyketide synthases in Aspergillus nidulans. J Am Chem Soc 134(19):8212–8221PubMedPubMedCentralCrossRefGoogle Scholar
  3. al Fahad A, Abood A, Simpson TJ, Cox RJ (2014a) The biosynthesis and catabolism of the maleic anhydride moiety of stipitatonic acid. Angew Chem Int Ed Engl 53(29):7519–7523PubMedCrossRefGoogle Scholar
  4. al Fahad A, Abood A, Fisch KM et al (2014b) Oxidative dearomatisation: the key step of sorbicillinoid biosynthesis. Chem Sci 5(2):523–527PubMedCrossRefGoogle Scholar
  5. Alberts AW, Chen J, Kuron G et al (1980) Mevinolin: a highly potent competitive inhibitor of hydroxymethylglutaryl-coenzyme A reductase and a cholesterol-lowering agent. Proc Natl Acad Sci USA 77(7):3957–3961PubMedPubMedCentralCrossRefGoogle Scholar
  6. Andrade R, Ayer WA, Mebe Paul P (1992) The metabolites of Trichoderma longibrachiatum. Part 1. Isolation of the metabolites and the structure of trichodimerol. Can J Chem 70(10):2526–2535CrossRefGoogle Scholar
  7. Anke T, Oberwinkler F, Steglich W, Schramm G (1977) Strobilurins - new antifungal antibiotics from Basidiomycete Strobilurus tenacellus (Pers Ex Fr) Sing. J Antibiot 30(10):806–810PubMedCrossRefGoogle Scholar
  8. Bailey AM, Cox RJ, Harley K et al (2007) Characterisation of 3-methylorcinaldehyde synthase (MOS) in Acremonium strictum: first observation of a reductive release mechanism during polyketide biosynthesis. Chem Commun (39):4053–4055Google Scholar
  9. Bailey AM, Fisch KM, Skellam E et al (2010) Catalytic role of the C-terminal domains of a fungal non-reducing polyketide synthase. Chem Commun 46(29):5331–5333CrossRefGoogle Scholar
  10. Bate C, Salmona M, Diomede L, Williams A (2004) Squalestatin cures prion-infected neurons and protects against prion neurotoxicity. J Biol Chem 279(15):14983–14990PubMedCrossRefGoogle Scholar
  11. Baxter A, Fitzgerald BJ, Hutson JL et al (1992) Squalestatin 1, a potent inhibitor of squalene synthase, which lowers serum cholesterol in vivo. J Biol Chem 267(17):11705–11708PubMedGoogle Scholar
  12. Beck J, Ripka S, Siegner A et al (1990) The multifunctional 6-methylsalicylic acid synthase gene of Penicillium patulum - its gene structure relative to that of other polyketide synthases. Eur J Biochem 192:487–498PubMedCrossRefGoogle Scholar
  13. Bennett JW, Klich M (2003) Mycotoxins. Clin Microbiol Rev 16(3):497–516PubMedPubMedCentralCrossRefGoogle Scholar
  14. Bérdy J (2005) Bioactive microbial metabolites. J Antibiot 58(1):1–26PubMedCrossRefGoogle Scholar
  15. Berger W, Micksche M, Elbling L (1997) Effects of multidrug resistance-related ATP-binding-cassette transporter proteins on the cytoskeletal activity of cytochalasins. Exp Cell Res 237(2):307–317PubMedCrossRefGoogle Scholar
  16. Bergmann S, Schümann J, Scherlach K et al (2007) Genomics-driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans. Nat Chem Biol 3(4):213–217PubMedCrossRefGoogle Scholar
  17. Bergstrom JD, Dufresne C et al (1995) Discovery, biosynthesis, and mechanism of action of the zaragozic acids: potent inhibitors of squalene synthase. Annu Rev Microbiol 49(1):607–639PubMedCrossRefGoogle Scholar
  18. Bingle LEH, Simpson TJ, Lazarus CM (1999) Ketosynthase domain probes identify two subclasses of fungal polyketide synthase genes. Fungal Genet Biol 26:209–223PubMedCrossRefGoogle Scholar
  19. Birch AJ, Massywestropp RA, Moye CJ (1955) Studies in relation to biosynthesis 7. 2-Hydroxy-6-methylbenzoic acid in Penicillium griseofulvum Dierckx. Aust J Chem 8(4):539–544CrossRefGoogle Scholar
  20. Birkinshaw JH, Raistrick H (1932) Studies in the biochemistry of micro-organisms: puberulic acid C(8)H(6)O(6) and an acid C(8)H(4)O(6), new products of the metabolism of glucose by Penicillium puberulum Bainier and Penicillium aurantiovirens Biourge. with an appendix on certain dihydroxybenzenedicarboxylic acids. Biochem J 26(2):441–453PubMedPubMedCentralCrossRefGoogle Scholar
  21. Blanc PJ, Laussac JP, Lebars J et al (1995) Characterization of monascidin A from Monascus as citrinin. Int J Food Microbiol 27(2-3):201–213PubMedCrossRefGoogle Scholar
  22. Boecker S, Zobel S, Meyer V, Süssmuth RD (2016) Rational biosynthetic approaches for the production of new-to-nature compounds in fungi. Fungal Genet Biol 89:89–101PubMedCrossRefGoogle Scholar
  23. Bonsch B, Belt V, Bartel C et al (2016) Identification of genes encoding squalestatin S1 biosynthesis and in vitro production of new squalestatin analogues. Chem Commun 52:6777–6780CrossRefGoogle Scholar
  24. Bradley JR (2008) TNF-mediated inflammatory disease. J Pathol 214(2):149–160PubMedCrossRefGoogle Scholar
  25. Braunberg RC, Gantt O, Barton C, Friedman L (1992) In vitro effects of the nephrotoxins ochratoxin A and citrinin upon biochemical function of porcine kidney. Arch Environ Contam Tocicol 22:464–470CrossRefGoogle Scholar
  26. Brown DW, Proctor RH (2016) Insights into natural products biosynthesis from analysis of 490 polyketide synthases from Fusarium. Fungal Genet Biol 89:37–51PubMedCrossRefGoogle Scholar
  27. Cacho RA, Tang Y, Chooi Y-H (2015) Next-generation sequencing approach for connecting secondary metabolites to biosynthetic gene clusters in fungi. Front Microbiol 5(e98212)Google Scholar
  28. Carver TJ, Rutherford KM, Berriman M et al (2005) ACT: the Artemis comparison tool. Bioinformatics 21(16):3422–3423PubMedCrossRefGoogle Scholar
  29. Challis GL, Ravel J, Townsend CA (2000) Predictive, structure-based model of amino acid recognition by nonribosomal peptide synthetase adenylation domains. Chem Biol 7:211–224PubMedCrossRefGoogle Scholar
  30. Chao T-C, Maxwell SM, Wong S-Y (1991) An outbreak of aflatoxicosis and boric acid poisoning in Malaysia: a clinicopathological study. J Pathol 164(3):225–233PubMedCrossRefGoogle Scholar
  31. Chiang Y-M, Oakley CE, Ahuja M et al (2013) An efficient system for heterologous expression of secondary metabolite genes in Aspergillus nidulans. J Am Chem Soc 135(20):7720–7731PubMedPubMedCentralCrossRefGoogle Scholar
  32. Cox RJ (2007) Polyketides, proteins and genes in fungi: programmed nano-machines begin to reveal their secrets. Org Biomol Chem 5(13):2010–2026PubMedCrossRefGoogle Scholar
  33. Cox RJ (2014) Oxidative rearrangements during fungal biosynthesis. Nat Prod Rep 31(10):1405–1424PubMedCrossRefGoogle Scholar
  34. Cox RJ, Glod F, Hurley D et al (2004) Rapid cloning and expression of a fungal polyketide synthase gene involved in squalestatin biosynthesis. Chem Commun (Camb) (20):2260–2261Google Scholar
  35. Crawford JM, Dancy BCR, Hill EA et al (2006) Identification of a starter unit acyl-carrier protein transacylase domain in an iterative type I polyketide synthase. Proc Natl Acad Sci USA 103(45):16728–16733PubMedPubMedCentralCrossRefGoogle Scholar
  36. Crawford JM, Thomas PM et al (2008) Deconstruction of Iterative multidomain polyketide synthase function. Science 320(5873):243–246PubMedPubMedCentralCrossRefGoogle Scholar
  37. Davison J, al Fahad A, Cai M et al (2012) Genetic, molecular, and biochemical basis of fungal tropolone biosynthesis. Proc Natl Acad Sci USA 109(20):7642–7647PubMedPubMedCentralCrossRefGoogle Scholar
  38. Dobias J, Betina V, Nemec P (1980) Insecticidal activity of ramihyfin-A, citrinin and rugulosin. Biologia 35(6):431–434Google Scholar
  39. Dufosse L (2006) Microbial production of food grade pigments. Food Technol Biotechnol 44(3):313–321Google Scholar
  40. Dufosse L, Fouillaud M, Caro Y et al (2014) Filamentous fungi are large-scale producers of pigments and colorants for the food industry. Curr Opin Biotechnol 26:56–61PubMedCrossRefGoogle Scholar
  41. Eley KL, Halo LM, Song Z et al (2007) Biosynthesis of the 2-pyridone tenellin in the insect pathogenic fungus Beauveria bassiana. ChemBioChem 8(3):289–297PubMedCrossRefGoogle Scholar
  42. El-Nezami H, Polychronaki N, Salminen S, Mykkanen H (2002) Binding rather than metabolism may explain the interaction of two food-grade Lactobacillus strains with zearalenone and its derivative alpha-zearalenol. Appl Environ Microbiol 68(7):3545–3549PubMedPubMedCentralCrossRefGoogle Scholar
  43. Fedorova ND, Moktali V, Medema MH (2012) Bioinformatics approaches and software for detection of secondary metabolic gene clusters. Methods Mol Biol 944:23–45PubMedGoogle Scholar
  44. Feher M, Schmidt JM (2003) Property distributions: differences between drugs, natural products, and molecules from combinatorial chemistry. J Chem Inf Comp Sci 43(1):218–227CrossRefGoogle Scholar
  45. Fisch KM, Bailey AM, Bakeer W et al (2011) Rational domain swaps decipher programming in fungal highly reducing polyketide synthases and resurrect an extinct metabolite. J Am Chem Soc 133(41):16635–16641PubMedCrossRefGoogle Scholar
  46. Foissner I, Wasteneys GO (2007) Wide-ranging effects of eight cytochalasins and latrunculin A and B on intracellular motility and actin filament reorganization in characean internodal cells. Plant Cell Physiol 48(4):585–597PubMedCrossRefGoogle Scholar
  47. Fujii I, Ono Y, Tada H et al (1996) Cloning of the polyketide synthase gene atX from Aspergillus terreus and its identification as the 6-methylsalicylic acid synthase gene by heterologous expression. Mol Gen Genet 253:1–10PubMedCrossRefGoogle Scholar
  48. Fujii R, Minami A, Gomi K, Oikawa H (2013) Biosynthetic assembly of cytochalasin backbone. Tetrahedron Lett 54(23):2999–3002CrossRefGoogle Scholar
  49. Gaffoor I, Brown DW, Plattner R et al (2005) Functional analysis of the polyketide synthase genes in the filamentous fungus Gibberella zeae (Anamorph Fusarium graminearum). Eukaryot Cell 4(11):1926–1933PubMedPubMedCentralCrossRefGoogle Scholar
  50. Galagan JE, Calvo SE et al (2003) The genome sequence of the filamentous fungus Neurospora crassa. Nature 422:859–868PubMedCrossRefGoogle Scholar
  51. Gelderblom WC, Jaskiewicz AK et al (1988) Fumonisins–novel mycotoxins with cancer-promoting activity produced by Fusarium moniliforme. Appl Environ Microbiol 54:1806–1811PubMedPubMedCentralGoogle Scholar
  52. George TP, Cook HW et al (1991) Inhibition of phosphatidylcholine and phosphatidylethanolamine biosynthesis by cytochalasin B in cultured glioma cells: potential regulation of biosynthesis by Ca2+-dependent mechanisms. Biochim Biophys Acta Lipids Lipid Metab 1084:185–193CrossRefGoogle Scholar
  53. Goldman L, Schwarz J et al (1960) Current status of griseofulvin: report on one hundred seventy-five cases. J Am Med Assoc 172:532–538CrossRefGoogle Scholar
  54. Gomez BL, Nosanchuk JD (2003) Melanin and fungi. Curr Opin Infect Dis 16:91–96PubMedCrossRefGoogle Scholar
  55. Halo LM, Heneghan MN et al (2008a) Late stage oxidations during the biosynthesis of the 2-pyridone tenellin in the entomopathogenic fungus Beauveria bassiana. J Am Chem Soc 130:17988–17996PubMedCrossRefGoogle Scholar
  56. Halo LM, Marshall JW et al (2008b) Authentic heterologous expression of the tenellin iterative polyketide synthase nonribosomal peptide synthetase requires coexpression with an enoyl reductase. ChemBioChem 9:585–594PubMedCrossRefGoogle Scholar
  57. Harrison LR, Colvin BM et al (1990) Pulmonary edema and hydrothorax in swine produced by fumonisin B1, a toxic metabolite of Fusarium moniliforme. J Vet Diagn Invest 2:217–221PubMedCrossRefGoogle Scholar
  58. He Y, Cox RJ (2016) The molecular steps of citrinin biosynthesis in fungi. Chem Sci 7:2119–2127CrossRefGoogle Scholar
  59. Hendrickson L, Davis C et al (1999) Lovastatin biosynthesis in Aspergillus terreus: characterization of blocked mutants, enzyme activities and a multifunctional polyketide synthase gene. Chem Biol 6:429–439PubMedCrossRefGoogle Scholar
  60. Hetherington C, Raistrick H (1931) On the production and chemical constitution of a new yellow colouring matter, citrinin, produced from glucose by Penicillium citrinum Thom. Philos Trans R Soc B 220:269–295CrossRefGoogle Scholar
  61. Hirose T, Izawa Y et al (1990) The effects of new cytochalasins from Phomopsis sp. and the derivatives on cellular structure and actin polymerization. Chem Pharm Bull 38:971–974PubMedCrossRefGoogle Scholar
  62. Hodge EG, Hidy PH, and Wehrmeister HJ (1966) Estrogenic compounds and animal growth promoters. US Patent 3239345Google Scholar
  63. Hu Y, Dietrich D et al (2014) A carbonate-forming Baeyer-Villiger monooxygenase. Nat Chem Biol 10:552–554PubMedPubMedCentralCrossRefGoogle Scholar
  64. Huitt-Roehl CR, Hill EA et al (2015) Starter unit flexibility for engineered product synthesis by the nonreducing polyketide synthase PksA. ACS Chem Biol 10:1443–1449PubMedPubMedCentralCrossRefGoogle Scholar
  65. Hunter S, Jones P et al (2012) InterPro in 2011: new developments in the family and domain prediction database. Nucleic Acids Res 40:4725–4725PubMedCentralCrossRefGoogle Scholar
  66. Isaka M, Tanticharoen M, Thebtaranonth Y (2000) Cordyanhydrides A and B. Two unique anhydrides from the insect pathogenic fungus Cordyceps pseudomilitaris BCC 1620. Tetrahedron Lett 41:1657–1660CrossRefGoogle Scholar
  67. Jenni S, Leibundgut M et al (2007) Structure of fungal fatty acid synthase and implications for iterative substrate shuttling. Science 316:254–261PubMedCrossRefGoogle Scholar
  68. Jung H, Kim C et al (2003) Color characteristics of Monascus pigments derived by fermentation with various amino acids. J Agric Food Chem 51:1302–1306PubMedCrossRefGoogle Scholar
  69. Kakule TB, Lin Z, Schmidt EW (2014) Combinatorialization of fungal polyketide synthase–peptide synthetase hybrid proteins. J Am Chem Soc 136:17882–17890PubMedCrossRefGoogle Scholar
  70. Khaldi N, Seifuddin FT et al (2010) SMURF: genomic mapping of fungal secondary metabolite clusters. Fungal Genet Biol 47:736–741PubMedPubMedCentralCrossRefGoogle Scholar
  71. Khayatt BI, Overmars L et al (2013) Classification of the adenylation and acyl-transferase activity of NRPS and PKS systems using ensembles of substrate specific hidden Markov models. PLoS One 8Google Scholar
  72. Kroken S, Glass NL et al (2003) Phylogenomic analysis of type I polyketide synthase genes in pathogenic and saprobic ascomycetes. Proc Natl Acad Sci USA 100:15670–15675PubMedPubMedCentralCrossRefGoogle Scholar
  73. Kurtz HJ, Mirocha J (1978) Mycotoxic fungi, mycotoxins, mycotoxicoses, vol 2. Marcel Dekker, New York, NYGoogle Scholar
  74. Lee TV, Johnson RD et al (2015) Prediction of the substrate for nonribosomal peptide synthetase (NRPS) adenylation domains by virtual screening. Proteins Struct Funct Bioinformatics 83:2052–2066CrossRefGoogle Scholar
  75. Li Y, Chooi YH et al (2011) Comparative characterization of fungal anthracenone and naphthacenedione biosynthetic pathways reveals an α-hydroxylation-dependent claisen-like cyclization catalyzed by a dimanganese thioesterase. J Am Chem Soc 133:15773–15785PubMedPubMedCentralCrossRefGoogle Scholar
  76. Li YF, Tsai KJS et al (2016) Comprehensive curation and analysis of fungal biosynthetic gene clusters of published natural products. Fungal Genet Biol 89:18–28PubMedPubMedCentralCrossRefGoogle Scholar
  77. Liu X, Walsh CT (2009) Cyclopiazonic acid biosynthesis in Aspergillus sp.: characterization of a reductase-like R* domain in cyclopiazonate synthetase that forms and releases cyclo-AcetoacetylL-tryptophan. Biochemistry 48:8746–8757PubMedPubMedCentralCrossRefGoogle Scholar
  78. Liu T, Chiang YM et al (2011) Engineering of an “unnatural” natural product by swapping polyketide synthase domains in Aspergillus nidulans. J Am Chem Soc 133:13314–13316PubMedPubMedCentralCrossRefGoogle Scholar
  79. Liu T, Sanchez JF et al (2014) Rational domain swaps reveal insights about chain length control by ketosynthase domains in fungal nonreducing polyketide synthases. Org Lett 16:1676–1679PubMedPubMedCentralCrossRefGoogle Scholar
  80. Liu L, Zhang Z et al (2015) Bioinformatical analysis of the sequences, structures and functions of fungal polyketide synthase product template domains. Sci Rep 5(10463)Google Scholar
  81. Ma SM, Li JW et al (2009) Complete reconstitution of a highly reducing iterative polyketide synthase. Science 326:589–592PubMedPubMedCentralCrossRefGoogle Scholar
  82. Maier T, Leibundgut M, Ban N (2008) The crystal structure of a mammalian fatty acid synthase. Science 321:1315–1322PubMedCrossRefGoogle Scholar
  83. Makioka A, Kumagai M et al (2004) Different effects of cytochalasins on the growth and differentiation of Entamoeba invadens. Parasitol Res 93:68–71PubMedCrossRefGoogle Scholar
  84. Malpartida F, Hopwood DA (1984) Molecular cloning of the whole biosynthetic pathway of a Streptomyces antibiotic and its expression in a heterologous host. Nature 309:462–464PubMedCrossRefGoogle Scholar
  85. Mandala SM, Thornton RA et al (1997) Viridiofungins, novel inhibitors of sphingolipid synthesis. J Antibiot 50:339–343PubMedCrossRefGoogle Scholar
  86. Marasas WF, Kellerman TS et al (1988) Leukoencephalomalacia in a horse induced by fumonisin B1 isolated from Fusarium moniliforme. J Vet Res 55:197–203Google Scholar
  87. Mayorga ME, Timberlake WE (1990) Isolation and molecular characterization of the Aspergillus nidulans wA gene. Genetics 126:73–79PubMedPubMedCentralGoogle Scholar
  88. Mayorga ME, Timberlake WE (1992) The developmentally regulated Aspergillus nidulans wA gene encodes a polypeptide homologous to polyketide and fatty acid synthases. Mol Gen Genet 235:205–212PubMedCrossRefGoogle Scholar
  89. McCapra F, Scott AI et al (1964) The constitution of monorden, an antibiotic with tranquilising action. Tetrahedron Lett 15:869–875CrossRefGoogle Scholar
  90. Medema MH, Blin K et al (2011) antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences. Nucleic Acids Res 39:W339–W346PubMedPubMedCentralCrossRefGoogle Scholar
  91. Medema MH, Kottmann R et al (2015) Minimum information about a biosynthetic gene cluster. Chem Biol 11:625–631Google Scholar
  92. Minowa Y, Araki M, Kanehisa M (2007) Comprehensive analysis of distinctive polyketide and nonribosomal peptide structural motifs encoded in microbial genomes. J Mol Biol 368:1500–1517PubMedCrossRefGoogle Scholar
  93. Moriguchi T, Ebizuka YY, Fujii I (2008) Domain-domain interactions in the iterative type I polyketide synthase ATX from Aspergillus terreus. ChemBioChem 9:1207–1212PubMedCrossRefGoogle Scholar
  94. Nakayashiki H, Hanada S, Quoc NB, Kadotani N, Tosa Y, Mayama S (2005) RNA silencing as a tool for exploring gene function in ascomycete fungi. Fungal Genet Biol 42:275–283PubMedCrossRefGoogle Scholar
  95. Newman AG, Vagstad AL, Belecki K, Scheerer JR, Townsend CA (2012) Analysis of the cercosporin polyketide synthase CTB1 reveals a new fungal thioesterase function. Chem Commun 48:11772–11774CrossRefGoogle Scholar
  96. Newman AG, Vagstad AL, Storm PA, Townsend CA (2014) Systematic domain swaps of iterative, nonreducing polyketide synthases provide a mechanistic understanding and rationale for catalytic reprogramming. J Am Chem Soc 136:7348–7362PubMedPubMedCentralCrossRefGoogle Scholar
  97. 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 8:157–178PubMedCrossRefGoogle Scholar
  98. Niehaus E-M, Kleigrewe K, Wiemann P, Studt L, Sieber CMK, Connolly LR, Freitag M, Güldener U, Tudzynski B, Humpf H-U (2013) Genetic manipulation of the Fusarium fujikuroi fusarin gene cluster yields insight into the complex regulation and fusarin biosynthetic pathway. Chem Biol 20:1055–1066PubMedCrossRefGoogle Scholar
  99. Nordberg H, Cantor M, Dusheyko S, Hua S, Poliakov A, Shabalov I, Smirnova T, Grigoriev IV, Dubchak I (2014) The genome portal of the Department of Energy Joint Genome Institute: 2014 updates. Nucleic Acids Res 42:D26–D31PubMedCrossRefGoogle Scholar
  100. Patten PC (1981) Aflatoxins and disease. Am J Trop Med Hyg 30:422–425PubMedCrossRefGoogle Scholar
  101. Peterson JR, Mitchison TJ (2002) Small molecules, big impact: a history of chemical inhibitors and the cytoskeleton. Chem Biol 9:1275–1285PubMedCrossRefGoogle Scholar
  102. Rampal AL, Pinkofsky HB, Jung CY (1998) Structure of cytochalasins and cytochalasin-B binding-sites in human-erythrocyte membranes. Biochemistry 19:679–683CrossRefGoogle Scholar
  103. Rees DO, Bushby N, Cox RJ, Harding JR, Simpson TJ, Willis CL (2007) Synthesis of [1,2-C-13(2), N-15]-L-homoserine and its incorporation by the PKS-NRPS system of Fusarium moniliforme into the mycotoxin fusarin C. ChemBioChem 8:46–50PubMedCrossRefGoogle Scholar
  104. Roettig M, Medema MH, Blin K, Weber T, Rausch C, Kohlbacher O (2011) NRPSpredictor2-a web server for predicting NRPS adenylation domain specificity. Nucleic Acids Res 39:W362–W367CrossRefGoogle Scholar
  105. Schofield JG (1971) Cytochalasin-B and release of growth hormone. Nat New Biol 234:215–216PubMedCrossRefGoogle Scholar
  106. Schulte TW, Akinaga S, Soga S, Sullivan W, Stensgard B, Toft D, Neckers LM (1998) Antibiotic radicicol binds to the N-terminal domain of Hsp90 and shares important biologic activities with geldanamycin. Cell Stress Chaperones 3:100–108PubMedPubMedCentralCrossRefGoogle Scholar
  107. 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 331:253–260PubMedCrossRefGoogle Scholar
  108. Sharma SV, Agatsuma T, Nakano H (1998) Targeting of the protein chaperone, HSP90, by the transformation suppressing agent, radicicol. Oncogene 16:2639–2645PubMedCrossRefGoogle Scholar
  109. Simpson TJ (1998) Application of isotopic methods to secondary metabolic pathways. Top Curr Chem 195:1–48CrossRefGoogle Scholar
  110. Solovyev V, Kosarev P, Seledsov I, Vorobyev D (2006) Automatic annotation of eukaryotic genes, pseudogenes and promoters. Genome Biol 7(suppl 1):S10PubMedPubMedCentralCrossRefGoogle Scholar
  111. Song Z, Cox RJ, Lazarus CM, Simpson TJ (2004) Fusarin C biosynthesis in Fusarium moniliforme and Fusarium venenatum. ChemBioChem 5:1196–1203PubMedCrossRefGoogle Scholar
  112. Squire RA (1981) Ranking animal carcinogens - a proposed regulatory approach. Science 214:877–880PubMedCrossRefGoogle Scholar
  113. Stachelhaus T, Mootz HD, Marahiel MA (1999) The specificity-conferring code of adenylation domains in nonribosomal peptide synthetases. Chem Biol 6:493–505PubMedCrossRefGoogle Scholar
  114. Sun H, Ho CL, Ding F, Soehano I, Liu X-W, Liang Z-X (2012) Synthesis of (R)-mellein by a partially reducing iterative polyketide synthase. J Am Chem Soc 134:11924–11927PubMedCrossRefGoogle Scholar
  115. Sydenham EW, Shephard GS, Thiel PG, Marasas WFO, Stockenstrom S (1991) Fumonisin contamination of commercial corn-based human foodstuffs. J Agric Food Chem 39:2014–2018CrossRefGoogle Scholar
  116. Szwalbe AJ, Williams K, O'Flynn DE, Bailey AM, Mulholland NP, Vincent JL, Willis CL, Cox RJ, Simpson TJ (2015) Novel nonadride, heptadride and maleic acid metabolites from the byssochlamic acid producer Byssochlamys fulva IMI 40021-an insight into the biosynthesis of maleidrides. Chem Commun 51:17088–17091CrossRefGoogle Scholar
  117. Tilburn J, Roussel F, Scazzocchio C (1990) Insertional inactivation and cloning of the wA-gene of Aspergillus nidulans. Genetics 126:81–90PubMedPubMedCentralGoogle Scholar
  118. Udwary DW, Merski M, Townsend CA (2002) A method for prediction of the locations of linker regions within large multifunctional proteins, and application to a type I polyketide synthase. J Mol Biol 323:585–598PubMedPubMedCentralCrossRefGoogle Scholar
  119. Ugai T, Minami A, Fujii R, Tanaka M, Oguri H, Gomi K, Oikawa H (2015) Heterologous expression of highly reducing polyketide synthase involved in betaenone biosynthesis. Chem Commun 51:1878–1188CrossRefGoogle Scholar
  120. Van Dijk EL, Auger H, Jaszczyszyn Y, Thermes C (2014) Ten years of next-generation sequencing technology. Trends Genet 30:418–426PubMedCrossRefGoogle Scholar
  121. van Egmond HP (1989) Aflatoxin M1: occurrence, toxicity, regulation. In: van Egmond HP (ed) Mycotoxins in dairy products. Elsevier Applied Science, London, pp 11–55Google Scholar
  122. Warr GA, Veitch JA, Walsh AW, Hesler GA, Pirnik DM, Leet JE, Lin P-FM, Medina IA, McBrien KD, Forenza S, Clark JM, Lam KS (1996) BMS-182123, a fungal metabolite that inhibits the production of TNF-alpha by macrophages and monocytes. J Antibiot 49:234–240PubMedCrossRefGoogle Scholar
  123. Wasil Z, Pahirulzaman KAK, Butts C, Simpson TJ, Lazarus CM, Cox RJ (2013) One pathway, many compounds: heterologous expression of a fungal biosynthetic pathway reveals its intrinsic potential for diversity. Chem Sci 4:3845–3856CrossRefGoogle Scholar
  124. Weber T, Blin K, Duddela S, Krug D, Kim HU, Bruccoleri R, Lee SY, Fischbach MA, Mueller R, Wohlleben W, Breitling R, Takano E, Medema MH (2015) antiSMASH 3.0-a comprehensive resource for the genome mining of biosynthetic gene clusters. Nucleic Acids Res 43:W237–W243PubMedPubMedCentralCrossRefGoogle Scholar
  125. Weld RJ, Plummer KM, Carpenter MA, Ridgway HJ (2006) Approaches to functional genomics in filamentous fungi. Cell Res 16:31–44PubMedCrossRefGoogle Scholar
  126. Williams JA, Wolff J (1971) Cytochalasin B inhibits thyroid secretion. Biochem Biophys Res Commun 44:422–425PubMedCrossRefGoogle Scholar
  127. Williams JH, Phillips TD, Jolly PE, Stiles JK, Jolly CM, Aggarwal D (2004) Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions. Am J Clin Nutr 80:106–1122Google Scholar
  128. Williams K, Szwalbe AJ, Mulholland NP, Vincent JL, Bailey AM, Willis CL, Simpson TJ, Cox RJ (2016) Heterologous production of fungal maleidrides reveals the cryptic cyclization involved in their biosynthesis. Angew Chem Int Ed 55:6784–6788CrossRefGoogle Scholar
  129. Winssinger N, Barluenga S (2007) Chemistry and biology of resorcylic acid lactones. Chem Commun 7:22–36CrossRefGoogle Scholar
  130. Woo PCY, Lam C-W, Tam EWT, Leung CKF, Wong SSY, Lau SKP, Yuen K-W (2012) First discovery of two polyketide synthase genes for mitorubrinic acid and mitorubrinol yellow pigment biosynthesis and implications in virulence of Penicillium marneffei. PLoS Neglect Trop Dis 6:e1871CrossRefGoogle Scholar
  131. Xu Y, Zhou T, Zhou Z, Su S, Roberts SA, Montfort WR, Zeng J, Chen M, Zhang W, Lin M, Zhan J, Molnar I (2013a) Rational reprogramming of fungal polyketide first-ring cyclization. Proc Natl Acad Sci USA 110:5398–5403PubMedPubMedCentralCrossRefGoogle Scholar
  132. Xu Y, Zhou T, Zhang S, Xuan L-J, Zhan J, Molnar I (2013b) Thioesterase domains of fungal nonreducing polyketide synthases act as decision gates during combinatorial biosynthesis. J Am Chem Soc 135:10783–10791PubMedPubMedCentralCrossRefGoogle Scholar
  133. Xu Y, Zhou T, Zhang S, Espinosa-Artiles P, Wang L, Zhang W, Lin M, Gunatilaka AAL, Zhan J, Molnar I (2014) Diversity-oriented combinatorial biosynthesis of benzenediol lactone scaffolds by subunit shuffling of fungal polyketide synthases. Proc Natl Acad Sci USA 111:12354–12359PubMedPubMedCentralCrossRefGoogle Scholar
  134. Yadav G, Gokhale RS, Mohanty B (2003) Computational approach for prediction of domain organization and substrate specificity of modular polyketide synthases. J Mol Biol 328:335–363PubMedCrossRefGoogle Scholar
  135. Yadav G, Gokhale RS, Mohanty B (2009) Towards prediction of metabolic products of polyketide synthases: an in silico analysis. PLoS Comput Biol 5(e1000351):1–14Google Scholar
  136. Yalpani N, Altier AJ, Barbour E, Cigan AL, Scelonge CJ (2001) Production of 6-methylsalicyclic acid by expression of a fungal polyketide synthase activates disease resistance in tobacco. Plant Cell 13:1401–1409PubMedPubMedCentralCrossRefGoogle Scholar
  137. Yeh H-H, Chang S-L, Chiang Y-M, Bruno KS, Oakley BR, T-K W, Wang CCC (2013) Engineering fungal nonreducing polyketide synthase by heterologous expression and domain swapping. Org Lett 15:756–759PubMedPubMedCentralCrossRefGoogle Scholar
  138. Zabala AO, Chooi Y-H, Choi MS, Lin H-C, Tang Y (2014) Fungal polyketide synthase product chain-length control by partnering thiohydrolase. ACS Chem Biol 9:1576–1586PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Institute for Organic Chemistry and Biomolekulares Wirkstoffzentrum (BMWZ)Leibniz Universität HannoverHannoverGermany

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