Use of UHPLC high-resolution Orbitrap mass spectrometry to investigate the genes involved in the production of secondary metabolites in Aspergillus flavus

Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment

Volumn 32, Issue 10, 2015, Pages 1656-1673

  Arroyo Manzanares, Natalia ^a,b   Diana Di Mavungu, José ^a   Uka, Valdet ^a   Malysheva, Svetlana V ^a   Cary, Jeffrey W ^c   Ehrlich, Kenneth C ^c   Vanhaecke, Lynn ^a   Bhatnagar, Deepak ^c   De Saeger, Sarah ^a  

^a GHENT UNIVERSITY   (Belgium)

^b UNIVERSITY OF GRANADA   (Spain)

^c SOUTHERN REGIONAL RESEARCH CENTER   (United States)

Author keywords

Aspergillusspp; comparative metabolomics; gene function; high resolution mass spectrometry

Indexed keywords

AFLATOXINS; ASPERGILLUS; BIOMOLECULES; FOOD SAFETY; FUNGI; GENE EXPRESSION; GENES; KETONES; MASS SPECTROMETRY; METABOLISM; SPECTROMETRY; TRANSCRIPTION;

ANALYTICAL METHODOLOGY; ASPERGILLUS SPP; COMPARATIVE METABOLOMICS; DETECTION AND IDENTIFICATIONS; GENE FUNCTION; HIGH RESOLUTION MASS SPECTROMETRY; ORBITRAP MASS SPECTROMETRIES; SECONDARY METABOLITES;

METABOLITES;

2 PYRIDONE DERIVATIVE; FUNGAL EXTRACT; METHYLTRANSFERASE; OXIDOREDUCTASE; POLYKETIDE SYNTHASE; AFLATOXIN; BENZOPYRAN DERIVATIVE; FUNGAL PROTEIN; LEPORIN B; OMTA PROTEIN, ASPERGILLUS; PYRIDONE DERIVATIVE; TRANSCRIPTION FACTOR;

ARTICLE; ASPERGILLUS FLAVUS; BIOSYNTHESIS; CONTROLLED STUDY; FUNGAL GENE; FUNGAL METABOLISM; FUNGAL METABOLITE; FUNGAL STRAIN; GENE CLUSTER; GENE FUNCTION; GENETIC MANIPULATION; LEPE GENE; LIQUID CHROMATOGRAPH; MASS SPECTROMETER; MASS SPECTROMETRY; METABOLITE; NONHUMAN; OMTA GENE; ORDA GENE; PKSA GENE; PRE B LYMPHOCYTE; PRIORITY JOURNAL; SECONDARY METABOLISM; ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY; VELOCITY; CHEMISTRY; FOOD SAFETY; GENE EXPRESSION REGULATION; GENETICS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; ISOLATION AND PURIFICATION; METABOLISM; MULTIGENE FAMILY; MUTATION;

AFLATOXINS; ASPERGILLUS FLAVUS; BENZOPYRANS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; FOOD SAFETY; FUNGAL PROTEINS; GENE EXPRESSION REGULATION, FUNGAL; GENES, FUNGAL; HUMANS; MASS SPECTROMETRY; METHYLTRANSFERASES; MULTIGENE FAMILY; MUTATION; OXIDOREDUCTASES; POLYKETIDE SYNTHASES; PYRIDONES; TRANSCRIPTION FACTORS;

EID: 84942985962     PISSN: 19440049     EISSN: 19440057     Source Type: Journal    
DOI: 10.1080/19440049.2015.1071499     Document Type: Article

References (67)

1. W.A.Abia, B.Warth, M.Sulyok, R.Krska, A.N.Tchana, P.B.Njobeh, M.F.Dutton, P.F.Moundipa 2013. Determination of multi-mycotoxin occurrence in cereals, nuts and their products in Cameroon by liquid chromatography tandem mass spectrometry (LC-MS/MS). Food Control. 31:438–453.
2. F.Al-Taher, K.Banaszewski, L.Jackson, J.Zweigenbaum, D.Ryu, J.Cappozzo. 2013. Rapid method for the determination of multiple mycotoxins in wines and beers by LC-MS/MS using a stable isotope dilution assay. J Agr Food Chem. 61:2378–2384.
3. N.Arroyo-Manzanares, J.Diana Di Mavungu, V.Uka, L.Gámiz-Gracia, A.M.García-Campaña, S.De Saeger. 2015. An integrated targeted and untargeted approach for the analysis of ergot alkaloids in cereals using UHPLC – hybrid quadrupole time-of-flight MS. World Mycotoxin J. in press.
4. G.Assante, L.Camarda, R.Locci, L.Merlini, G.Nasini, E.Papadopoulos. 1981. Isolation and structure of red pigments from Aspergillus flavus and related species, grown on a differential medium. J Agr Food Chem. 29:785–787.
5. J.W.Bennett. 2010. Aspergillus: molecular biology and genomics. Norfolk: Caister Academic Press. Chapter 1: An overview of the genus Aspergillus; p. 1–17.
6. F.Berthiller, R.Schuhmacher, G.Buttinger, R.Krska. 2005. Rapid simultaneous determination of major type A- and B-trichothecenes as well as zearalenone in maize by high performance liquid chromatography-tandem mass spectrometry. J Chromatogr A. 1062:209–216.
7. N.Blaas, H.-U.Humpf. 2013. Structural profiling and quantitation of glycosyl inositol phosphoceramides in plants with fourier transform mass spectrometry. J Agric Food Chem. 61:4257–4269.
8. J.W.Cary, K.C.Ehrlich, J.M.Bland, B.G.Montalbano. 2006. The aflatoxin biosynthesis cluster gene, aflX, encodes an oxidoreductase involved in conversion of versicolorin A to demethylsterigmatocystin. Appl Environ Microb. 72:1096–1101.
9. J.W.Cary, P.Y.Harris-Coward, K.C.Ehrlich, J.Diana Di Mavungu, S.V.Malysheva, S.De Saeger, P.F.Dowd, S.Shantappa, S.L.Martens, A.M.Calvo. 2014. Functional characterization of a veA-dependent polyketide synthase gene in Aspergillus flavus necessary for the synthesis of asparasone, a sclerotium-specific pigment. Fungal Genet Biol. 64:25–35.
10. P.K.Chang, J.W.Cary, J.Yu, D.Bhatnagar, T.E.Cleveland. 1995. The Aspergillus parasiticus polyketide synthase gene pksA, a homolog of Aspergillus nidulans wA, is required for aflatoxin B1 biosynthesis. Mol Gen Genet. 248:270–277.
11. P.K.Chang, K.C.Ehrlich, J.E.Linz, D.Bhatnagar, T.E.Cleveland, J.W.Bennett. 1996. Characterization of the Aspergillus parasiticus niaD and niiA gene cluster. Current Genetics. 30:68–75.
12. P.Chankhamjon, D.Boettger-Schmidt, K.Scherlach, B.Urbansky, G.Lackner, D.Kalb, H.M.Dahse, D.Hoffmeister, C.Hertweck. 2014. Biosynthesis of the halogenated mycotoxin aspirochlorine in Koji mold involves a cryptic amino acid conversion. Angew Chem Int Ed. 53:13409–13413.
13. Commission Decision 2002/657/EC. 2002. Commission decision of 12 August 2002 implementing council directive 96/23/EC concerning the performance of analytical methods and the interpretation of results. Off J Eur Comm. L221:8–36.
14. P.J.Cotty, P.Bayman, D.S.Egel, K.S.Elias. 1994. Agriculture, aflatoxins and Aspergillus. Genus Aspergillus. 69:1–27.
15. M.De Boevre, J.Diana Di Mavungu, P.Maene, K.Audenaert, D.Deforce, G.Haesaert, M.Eeckhout, A.Callebaut, F.Berthiller, C.Van Peteghem, et al. 2012. Development and validation of an LC-MS/MS method for the simultaneous determination of deoxynivalenol, zearalenone, T-2-toxin and some masked metabolites in different cereals and cereal-derived food. Food Addit Contam: Part A. 29:819–835.
16. J.Diana Di Mavungu, S.Monbaliu, M.-L.Scippo, G.Maghuin-Rogister, Y.-J.Schneider, Y.Larondelle, A.Callebaut, J.Robbens, C.Van Peteghem, S.De Saeger. 2009. LC-MS/MS multi-analyte method for mycotoxin determination in food supplements. Food Addit Contam: Part A. 26:885–895.
17. E.N.Ediage, J.Diana Di Mavungu, M.L.Scippo, Y.J.Schneider, Y.Yarondelle, A.Callebaut, J.Robbens, C.Van Peteghem, S.De Saeger. 2011. Screening, identification and quantification of glucosinolates in black radish (Raphanus sativus L. niger) based dietary supplements using liquid chromatography coupled with a photodiode array and liquid chromatography - mass spectrometry. J Chromatogr A. 1218:4395–4405.
18. E.N.Ediage, J.Diana Di Mavungu, S.Song, A.Wu, C.Van Peteghem, S.De Saeger. 2012. A direct assessment of mycotoxin biomarkers in human urine samples by liquid chromatography tandem mass spectrometry. Anal Chim Acta. 741:58–69.
19. K.C.Ehrlich, L.L.ScharfensteinJr., B.G.Montalbano, P.-K.Chang. 2008. Are the genes nadA and norB involved in formation of Aflatoxin G1? Int J Mol Sci. 9:1717–1729.
20. K.C.Ehrlich, Q.Wei, D.Bhatnagar. 2010. Increased sensitivity of Aspergillus flavus and Aspergillus parasiticus aflatoxin biosynthesis polyketide synthase mutants to UVB light. World Mycotoxin J. 3:263–270.
21. R.R.Forseth, S.Amaike, D.Schwenk, K.J.Affeldt, D.Hoffmeister, F.C.Schroeder, N.P.Keller. 2013. Homologous NRPS-like gene clusters mediate redundant small-molecule biosynthesis in Aspergillus flavus. Angew Chem Int Ed. 52:1590–1594.
22. J.C.Frisvad, U.Thrane. 1987. Standardized high-performance liquid chromatography of 182 mycotoxins and other fungal metabolites based on alkylphenone retention indices and UV-VIS spectra (diode array detection). J Chromatogr A. 404:195–214.
23. R.T.Gallagher, B.J.Willson. 1979. Aflatrem, the tremorgenic mycotoxin from Aspergillus flavus. Mycopathol. 66:183–185.
24. D.R.Georgianna, N.D.Fedorova, J.L.Burroughs, A.L.Dolezal, J.W.Bok, S.Horowitz-Brown, C.P.Woloshuk, J.Yu, N.P.Keller, G.A.Payne. 2010. Beyond aflatoxin: four distinct expression patterns and functional roles associated with Aspergillus flavus secondary metabolism gene clusters. Mol Plant Pathol. 11:213–226.
25. J.B.Gloer, M.R.TePaske, J.S.Sima, D.T.Wicklow, P.F.Dowd. 1988. Antiinsectan aflavinine derivatives from the sclerotia of Aspergillus flavus. J Org Chem. 53:5457–5460.
26. C.J.Guo, W.W.Sun, K.S.Bruno, C.C.C.Wang. 2014. Molecular genetic characterization of terreic acid pathway in Aspergillus terreus. Org Lett. 16:5250–5253.
27. W.Hedgepeth, J.Dahl 2011. High speed LC/MS/MS analysis of mycotoxins. Thermo Fisher Scientific poster. [cited 2015 May 30]. Available from: http://www2.shimadzu.com/applications/LCMS/EAS_2011_LCMS_001.pdf
28. D.K.Holm, L.M.Petersen, A.Klitgaard, P.B.Knudsen, Z.D.Jarczynska, K.F.Nielsen, C.F.Gotfredsen, T.O.Larsen, U.H.Mortensen. 2014. Molecular and chemical characterization of the biosynthesis of the 6-MSA-derived meroterpenoid Yanuthone D in Aspergillus niger. Chem Biol. 21:519–529.
29. Q.Hu, R.J.Noll, H.Li, A.Makarov, M.Hardman, R.G.Cooks. 2005. The Orbitrap: a new mass spectrometer. J Mass Spectrom. 40:430–443.
30. S.-P.Ip, C.-T.Che. 2006. Determination of aflatoxins in Chinese medicinal herbs by high-performance liquid chromatography using immunoaffinity column cleanup Improvement of recovery. J Chromatogr A. 1135:241–244.
31. N.Khaldi, F.T.Seifuddin, G.Turner, D.Haft, W.C.Nierman, K.H.Wolfe, N.D.Fedorova. 2010. SMURF: Genomic mapping of fungal secondary metabolite clusters. Fungal Genet Biol. 47:736–741.
32. S.Kildgaard, M.Mansson, I.Dosen, A.Klitgaard, J.C.Frisvad, T.C.Larsen, K.F.Nielsen. 2014a. Accurate dereplication of bioactive secondary metabolites from marine-derived fungi by UHPLC-DAD-QTOFMS and a MS/HRMS library. Mar Drugs. 12:3681–3705.
33. A.Klitgaard, A.Iversen, M.R.Andersen, T.O.Larsen, J.C.Frisvad, K.F.Nielsen. 2014b. Aggressive dereplication using UHPLC–DAD–QTOF: screening extracts for up to 3000 fungal secondary metabolites. Anal Bioanal Chem. 406:1933–1943.
34. R.Krska, G.Stubbings, R.Macarthur, C.Crews. 2008. Simultaneous determination of six major ergot alkaloids and their epimers in cereals and foodstuffs by LC-MS-MS. Anal Bioanal Chem. 391:563–576.
35. O.Lacina, M.Zachariasova, J.Urbanova, M.Vaclavikova, T.Cajka, J.Hajslova. 2012. Critical assessment of extraction methods for the simultaneous determination of pesticide residues and mycotoxins in fruits, cereals, spices and oil seeds employing ultra-high performance liquid chromatography-tandem mass spectrometry. J Chromatogr A. 1262:8–18.
36. V.M.T.Lattanzio, M.Solfrizzo, S.Powers, A.Visconti. 2007. Simultaneous determination of aflatoxins, ochratoxin A and Fusarium toxins in maize by liquid chromatography/tandem mass spectrometry after multitoxin immunoaffinity cleanup. Rapid Comm Mass Sp. 21:3253–3261.
37. L.-W.Lee, C.-H.Chiou, J.E.Linz. 2002. Function of Native OmtA in vivo and expression and distribution of this protein in colonies of Aspergillus parasiticus. Appl Environ Microb. 68:5718–5727.
38. Z.Lei, D.V.Huhman, L.W.Sumner. 2011. Mass spectrometry strategies in metabolomics. J Biol Chem. 29:25435–25442.
39. A.Makarov, E.Denisov, A.Kholomeev, W.Balschun, O.Lange, K.Strupat, S.Horning. 2006. Performance evaluation of a hybrid linear ion trap/Orbitrap mass spectrometer. Anal Chem. 78:2113–2120.
40. S.V.Malysheva, N.Arroyo-Manzanares, J.W.Cary, K.C.Ehrlich, J.Vanden Bussche, L.Vanhaecke, D.Bhatnagar, J.Diana Di Mavungu, S.De Saeger. 2014. Identification of novel metabolites from Aspergillus flavus by high resolution and multiple stage mass spectrometry. Food Add Contam Part A. 31:1–10.
41. S.Moco, R.J.Bino, R.C.H.De Vos, J.Vervoort. 2007. Metabolomics technologies and metabolite identification. TrAC. 26:855–866.
42. H.G.J.Mol, P.Plaza-Bolanos, P.Zomer, T.C.de Rijk, A.A.Stolker, P.P.Mulder. 2008. Toward a generic extraction method for simultaneous determination of pesticides, mycotoxins, plant toxins, and veterinary drugs in feed and food matrixes. Anal Chem. 80:9450–9459.
43. S.Monbaliu, C.Van Poucke, C.Detavernier, F.Dumoulin, M.Van De Velde, E.Schoeters, S.Van Dyck, O.Averkieva, C.Van Peteghem, S.De Saeger. 2010. Occurrence of mycotoxins in feed as analyzed by a multi-mycotoxin LC-MS/MS method. J Agr Food Chem. 58:66–71.
44. M.J.Nicholson, A.Koulman, B.J.Monahan, B.L.Pritchard, G.A.Payne, B.Scott. 2009. Identification of two aflatrem biosynthesis gene loci in Aspergillus flavus and metabolic engineering of Penicillium paxilli to elucidate their function. App Env Microbiol. 75:7469–7481.
45. K.F.Nielsen, T.O.Larsen. 2015. The importance of mass spectrometry dereplication on fungal secondary analysis. Front Microbiol. 6:1–15.
46. H.Pan, W.Yang, Y.Zhang, M.Yang, R.Feng, W.Wu, D.Guo. 2015. An integrated strategy for the systematic characterization and discovery of new indole alkaloids from Uncaria rhynchophylla by UHPLC/DAD/LTQ-Orbitrap-MS. Anal Bioanal Chem. doi:10.1007/s00216-015-8777-0.
47. C.Rank, M.L.Klejnstrup, L.M.Petersen, S.Kildgaard, J.C.Frisvad, C.H.Gotfredsen, T.O.Larsen. 2012. Comparative chemistry of Aspergillus oryzae (RIB40) and A. flavus (NRRL 3357). Metabolites. 2:39–56.
48. Y.Ren, Y.Zhang, S.Shao, Z.Cai, L.Feng, H.Pan, Z.Wang. 2007. Simultaneous determination of multi-component mycotoxin contaminants in foods and feeds by ultra-performance liquid chromatography tandem mass spectrometry. J Chromatogr A. 1143:48–64.
49. T.Saruwatari, F.Yagishita, T.Mino, H.Noguchi, K.Hotta, K.Watanabe. 2014. Cytochrome P450 as dimerization catalyst in diketopiperazine alkaloid biosynthesis. ChemBioChem. 15:656–659.
50. Y.Seshime, P.Rao Juvvadi, M.Tokuoka, Y.Koyama, K.Kitamoto, Y.Ebizuka, I.Fujii. 2009. Functional expression of the Aspergillus flavus PKS–NRPS hybrid CpaA involved in the biosynthesis of cyclopiazonic acid. Bioorg Med Chem Lett. 19:3288–3292.
51. J.Smedsgaard. 1997. Micro-scale extraction procedure for standardized screening of fungal metabolite production in cultures. J Chromatogr A. 760:264–270.
52. B.B.Snider, Q.Lu. 1996. Total Synthesis of (±)-Leporin A. J Org Chem. 61:2839–2844.
53. J.P.Springer, G.Bűchi, B.Kobbe, A.L.Demain, J.Clardy. 1977. The structure of ditryptophenaline - a new metabolite of Aspergillus flavus. Tetrahed Lett. 18:2403–2406.
54. M.Sulyok, R.Krska, R.Schuhmacher. 2007. A liquid chromatography/tandem mass spectrometric multi-mycotoxin method for the quantification of 87 analytes and its application to semi-quantitative screening of moldy food samples. Anal Bioanal Chem. 389:1505–1523.
55. M.R.TePaske, J.B.Gloer, D.T.Wicklow, P.F.Dowd. 1990. Aflavazole: a new antiinsectan carbazole metabolite from the sclerotia of Aspergillus flavus. J Org Chem. 55:5299–5301.
56. M.R.TePaske, J.B.Gloer, D.T.Wicklow, P.F.Dowd. 1991. Leporin A: An antiinsectan N-alkoxypyridone from the sclerotia of Aspergillus leporis. Tetrahedron Lett. 32:5687–5690.
57. M.R.TePaske, J.B.Gloer, D.T.Wicklow, P.F.Dowd. 1992. Aflavarin and β-Aflatrem: new anti-insectan metabolites from the sclerotia of Aspergillus flavus. J Nat Prod. 55:1080–1086.
58. Y.Terabayashi, M.Sano, N.Yamane, J.Marui, K.Tamano, J.Sagara, M.Dohmoto, K.Oda, E.Ohshima, K.Tachibana, et al. 2010. Identification and characterization of genes responsible for biosynthesis of kojic acid, an industrially important compound from Aspergillus oryzae. Gungal Genet Biol. 47:953–961.
59. M.Umemura, N.Nagano, H.Koike, J.Kawano, T.Ishii, Y.Miyamura, M.Kikuchi, K.Tamano, J.Yu, K.Shin-ya, et al. 2014. Characterization of the biosynthetic gene cluster for the ribosomally synthesized cyclic peptide ustiloxin B in Aspergillus flavus. Fungal Genet Biol. 68:23–30.
60. L.Van Meulebroek, J.Vanden Bussche, N.De Clercq, K.Steppe, L.Vanhaecke. 2015. A metabolomics approach to unravel the regulating role of phytohormones towards carotenoid metabolism in tomato fruit. Metabolomics. 11:667–683.
61. E.Varga, T.Glauner, F.Berthiller, R.Krska, R.Schuhmacher, M.Sulyok. 2013. Development and validation of a (semi-)quantitative UHPLC-MS/MS method for the determination of 191 mycotoxins and other fungal metabolites in almonds, hazelnuts, peanuts and pistachios. Anal Bioanal Chem. 405:5087–5104.
62. A.Wieghaus, A.Makarov, U.Froehlich, M.Kellmann, E.Denisov, O.Lange. 2011. The thermo scientific exactive benchtop LC/MS Orbitrap mass spectrometer. Thermo Fisher Scientific. Application Note: 30162. [cited 2015 Jan 5]. Available from: http://www.thermo.com.cn/Resources/200811/2114225422.pdf
63. J.Y.Yang, L.M.Sanchez, C.M.Rath, X.Liu, P.D.Boudreau, N.Bruns, E.Glukhov, A.Wodtke, R.de Felicio, A.Fenner, et al. 2013. Molecular networking as a dereplication strategy. J Nat Prod. 76:1686–1699.
64. J.Yu, P.K.Chang, J.W.Cary, M.Wright, D.Bhatnagar, T.E.Cleveland, G.A.Payne, J.E.Linz. 1995. Comparative mapping of aflatoxin pathway gene clusters in Aspergillus parasiticus and Aspergillus flavus. Appl Environ Microbiol. 61:2365–2371.
65. J.Yu, C.Perng-Kuang, K.C.Ehrlich, J.W.Cary, D.Bhatnagar, T.E.Cleveland, G.A.Payne, J.E.Linz, C.P.Woloshuk, J.W.Bennett. 2004. Clustered pathway genes in aflatoxin biosynthesis. Appl Environ Microbiol. 70:1253–1262.
66. C.Zhang, L.Jin, B.Mondie, S.S.Mitchell, A.L.Castelhano, W.Cai, N.Bergenhem. 2003. Leporin B: a novel hexokinase II gene inducing agent from an unidentified fungus. Bioorg Med Chem Lett. 13:1433–1435.
67. S.Zhang, B.J.Monahan, J.S.Tkacz, B.Scott. 2004. Indole-diterpene gene cluster from Aspergillus flavus. App Env Microbiol. 70:6857–6883.