Biotechnological applications of functional metagenomics in the food and pharmaceutical industries

Frontiers in Microbiology

Volumn 6, Issue JUN, 2015, Pages

  Coughlan, Laura M ^a   Cotter, Paul D ^a,b   Hill, Colin ^b,c   Alvarez Ordóñez, Avelino ^a  

^a TEAGASC FOOD RESEARCH CENTRE   (Ireland)

^b UNIVERSITY COLLEGE CORK   (Ireland)

^c UNIVERSITY COLLEGE CORK   (Ireland)

Author keywords

Antimicrobials; Bioactives; Catalysts; Food; Functional metagenomics; Industrial applications; Pharmacological

Indexed keywords

ALKALINE PROTEINASE; AMOXICILLIN; AMPICILLIN; AMYLASE; ANTIINFECTIVE AGENT; BETA GLUCAN HYDROLASE; BETA LACTAMASE; BIOTIN; CARBOXYLESTERASE; CHITINASE; CHLORAMPHENICOL; GENOMIC DNA; GENTAMICIN; GLUCONOLACTONASE; GLYCOSIDASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; KANAMYCIN; METALLOPROTEINASE; MINOCYCLINE; PEDERIN; PENICILLIN DERIVATIVE; POLYKETIDE SYNTHASE; RIBOSOME RNA; RIFAMPICIN; RNA 16S; STREPTOMYCIN; TETRACYCLINE; TRANSCRIPTION FACTOR LUXR; UNINDEXED DRUG; XYLAN ENDO 1,3 BETA XYLOSIDASE;

ANTIBIOTIC SENSITIVITY; BIOCATALYST; BIOTECHNOLOGY; DRUG INDUSTRY; FLUORESCENCE ACTIVATED CELL SORTING; FOOD INDUSTRY; GENE EXPRESSION; GENE SEQUENCE; GENETIC ANALYSIS; GRAM NEGATIVE BACTERIUM; GRAM POSITIVE BACTERIUM; ISOPTERA; METAGENOMICS; MOLECULAR CLONING; NASUTITERMES; NONHUMAN; OSMOLARITY; PHENOTYPE; PHYLOGENY; REVIEW;

EID: 84937110120     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2015.00672     Document Type: Review

References (147)

1. Abumweis, S.S., Jew, S., and Ames, N.P. (2010). Beta-glucan from barley and its lipid-lowering capacity: a meta-analysis of randomized, controlled trials. Eur. J. Clin. Nutr. 64, 1472-1480. doi: 10.1038/ejcn.2010.178.
2. Alanis, A.J. (2005). Resistance to antibiotics: are we in the post-antibiotic era? Arch. Med. Res. 36, 697-705. doi: 10.1016/j.arcmed.2005.06.009.
3. Ashie, I.N. A., Sorensen, T.L., and Nielsen, P.M. (2002). Effects of papain and a microbial enzyme on meat proteins and beef tenderness. J. Food Sci. 67, 2138-2142. doi: 10.1111/j.1365-2621.2002.tb09516.x.
4. Banik, J.J., and Brady, S.F. (2010). Recent application of metagenomic approaches toward the discovery of antimicrobials and other bioactive small molecules. Curr. Opin. Microbiol. 13, 603-609. doi: 10.1016/j.mib.2010.08.012.
5. Bartoloni, A., Pallecchi, L., Rodriguez, H., Fernandez, C., Mantella, A., Bartalesi, F., et al. (2009). Antibiotic resistance in a very remote Amazonas community. Int. J. Antimicrob. Agents 33, 125-129. doi: 10.1016/j.ijantimicag.2008.07.029.
6. Bates, S.T., Berg-Lyons, D., Lauber, C.L., Walters, W.A., Knight, R., and Fierer, N. (2012). A preliminary survey of lichen associated eukaryotes using pyrosequencing. Lichenologist 44, 137-146. doi: 10.1017/S0024282911000648.
7. Berman, H.F., and Riley, L.W. (2013). Identification of novel antimicrobial resistance genes from microbiota on retail spinach. BMC Microbiol. 13:272. doi: 10.1186/1471-2180-13-272.
8. Bijtenhoorn, P., Mayerhofer, H., Muller-Dieckmann, J., Utpatel, C., Schipper, C., Hornung, C., et al. (2011). A novel metagenomic short-chain dehydrogenase/reductase attenuates Pseudomonas aeruginosa biofilm formation and virulence on Caenorhabditis elegans. PLoS ONE 6:e26278. doi: 10.1371/journal.pone.0026278.
9. Biver, S., Portetelle, D., and Vandenbol, M. (2013a). Characterization of a new oxidant-stable serine protease isolated by functional metagenomics. Springerplus 2:410. doi: 10.1186/2193-1801-2-410.
10. Biver, S., Steels, S., Portetelle, D., and Vandenbol, M. (2013b). Bacillus subtilis as a tool for screening soil metagenomic libraries for antimicrobial activities. J. Microbiol. Biotechnol. 23, 850-855. doi: 10.4014/jmb.1212.12008.
11. Biver, S., and Vandenbol, M. (2013). Characterization of three new carboxylic ester hydrolases isolated by functional screening of a forest soil metagenomic library. J. Ind. Microbiol. Biotechnol. 40, 191-200. doi: 10.1007/s10295-012-1217-7.
12. Boadi, D.K., and Neufeld, R.J. (2001). Encapsulation of tannase for the hydrolysis of tea tannins. Enzyme Microb. Technol. 28, 590-595. doi: 10.1016/S0141-0229(01)00295-2.
13. Bornscheuer, U.T. (2002). Microbial carboxyl esterases: classification, properties and application in biocatalysis. FEMS Microbiol. Rev. 26, 73-81. doi: 10.1111/j.1574-6976.2002.tb00599.x.
14. Brady, S.F., Chao, C.J., and Clardy, J. (2004). Long-chain N-acyltyrosine synthases from environmental DNA. Appl. Environ. Microbiol. 70, 6865-6870. doi: 10.1128/AEM.70.11.6865-6870.2004.
15. Brady, S.F., Chao, C.J., Handelsman, J., and Clardy, J. (2001). Cloning and heterologous expression of a natural product biosynthetic gene cluster from eDNA. Org. Lett. 3, 1981-1984. doi: 10.1021/ol015949k.
16. Brady, S.F., and Clardy, J. (2000). Long-chain N-acyl amino acid antibiotics isolated from heterologously expressed environmental DNA. J. Am. Chem. Soc. 122, 12903-12904. doi: 10.1021/ja002990u.
17. Brady, S.F., and Clardy, J. (2005). Cloning and heterologous expression of isocyanide biosynthetic genes from environmental DNA. Angew. Chem. Int. Ed Engl. 44, 7063-7065. doi: 10.1002/anie.200501941.
18. Cantarelli, C., Brenna, O., Giovanelli, G., and Rossi, M. (1989). Beverage stabilization through enzymatic removal of phenolics. Food Biotechnol. 3, 203-213. doi: 10.1080/08905438909549709.
19. Cecchini, D.A., Laville, E., Laguerre, S., Robe, P., Leclerc, M., Dore, J., et al. (2013). Functional metagenomics reveals novel pathways of prebiotic breakdown by human gut bacteria. PLoS ONE 8:e72766. doi: 10.1371/journal.pone.0072766.
20. Chandler, J.A., Thongsripong, P., Green, A., Kittayapong, P., Wilcox, B.A., Schroth, G.P., et al. (2014). Metagenomic shotgun sequencing of a Bunyavirus in wild-caught Aedes aegypti from Thailand informs the evolutionary and genomic history of the Phleboviruses. Virology 464-465, 312-319. doi: 10.1016/j.virol.2014.06.036.
21. Chang, F.Y., and Brady, S.F. (2013). Discovery of indolotryptoline antiproliferative agents by homology-guided metagenomic screening. Proc. Natl. Acad. Sci. U.S.A. 110, 2478-2483. doi: 10.1073/pnas.1218073110.
22. Cheng, F.S., Sheng, J.P., Cai, T., Jin, J., Liu, W.Z., Lin, Y.M., et al. (2012a). A protease-insensitive feruloyl esterase from China holstein cow rumen metagenomic library: expression, characterization, and utilization in ferulic acid release from wheat straw. J. Agric. Food Chem. 60, 2546-2553. doi: 10.1021/jf204556u.
23. Cheng, F.S., Sheng, J.P., Dong, R.B., Men, Y.J., Gan, L., and Shen, L. (2012b). Novel xylanase from a holstein cattle rumen metagenomic library and its application in xylooligosaccharide and ferulic acid production from wheat straw. J. Agric. Food Chem. 60, 12516-12524. doi: 10.1021/jf302337w.
24. Cheng, G., Hu, Y., Yin, Y., Yang, X., Xiang, C., Wang, B., et al. (2012c). Functional screening of antibiotic resistance genes from human gut microbiota reveals a novel gene fusion. FEMS Microbiol. Lett. 336, 11-16. doi: 10.1111/j.1574-6968.2012.02647.x.
25. Chu, X.M., He, H.Z., Guo, C.Q., and Sun, B.L. (2008). Identification of two novel esterases from a marine metagenomic library derived from South China Sea. Appl. Microbiol. Biotechnol. 80, 615-625. doi: 10.1007/s00253-008-1566-3.
26. Clemente, J.C., Pehrsson, E.C., Blaser, M.J., Sandhu, K., Gao, Z., Wang, B., et al. (2015). The microbiome of uncontacted Amerindians. Sci. Adv. 1:e1500183. doi: 10.1126/sciadv.1500183.
27. Cooper, M.A., and Shlaes, D. (2011). Fix the antibiotics pipeline. Nature 472, 32. doi: 10.1038/472032a.
28. Craig, J.W., Chang, F.Y., and Brady, S.F. (2009). Natural products from environmental DNA hosted in Ralstonia metallidurans. ACS Chem. Biol. 4, 23-28. doi: 10.1021/cb8002754.
29. Craig, J.W., Chang, F.Y., Kim, J.H., Obiajulu, S.C., and Brady, S.F. (2010). Expanding small-molecule functional metagenomics through parallel screening of broad-host-range cosmid environmental DNA libraries in diverse proteobacteria. Appl. Environ. Microbiol. 76, 1633-1641. doi: 10.1128/AEM. 02169-09.
30. Culligan, E.P., Sleator, R.D., Marchesi, J.R., and Hill, C. (2012). Functional metagenomics reveals novel salt tolerance loci from the human gut microbiome. ISME J. 6, 1916-1925. doi: 10.1038/ismej.2012.38.
31. Culligan, E.P., Sleator, R.D., Marchesi, J.R., and Hill, C. (2013). Functional environmental screening of a metagenomic library identifies stlA; a unique salt tolerance locus from the human gut microbiome. PLoS ONE 8:e82985. doi: 10.1371/journal.pone.0082985.
32. Devirgiliis, C., Zinno, P., Stirpe, M., Barile, S., and Perozzi, G. (2014). Functional screening of antibiotic resistance genes from a representative metagenomic library of food fermenting microbiota. Biomed Res. Int. 2014:290967. doi: 10.1155/2014/290967.
33. Donato, J.J., Moe, L.A., Converse, B.J., Smart, K.D., Berklein, F.C., McManus, P.S., et al. (2010). Metagenomic analysis of apple orchard soil reveals antibiotic resistance genes encoding predicted bifunctional proteins. Appl. Environ. Microbiol. 76, 4396-4401. doi: 10.1128/AEM. 01763-09.
34. Elend, C., Schmeisser, C., Hoebenreich, H., Steele, H.L., and Streit, W.R. (2007). Isolation and characterization of a metagenome-derived and cold-active lipase with high stereospecificity for (R)-ibuprofen esters. J. Biotechnol. 130, 370-377. doi: 10.1016/j.jbiotec.2007.05.015.
35. Elend, C., Schmeisser, C., Leggewie, C., Babiak, P., Carballeira, J.D., Steele, H.L., et al. (2006). Isolation and biochemical characterization of two novel metagenome-derived esterases. Appl. Environ. Microbiol. 72, 3637-3645. doi: 10.1128/AEM.72.5.3637-3645.2006.
36. Entcheva, P., Liebl, W., Johann, A., Hartsch, T., and Streit, W.R. (2001). Direct cloning from enrichment cultures, a reliable strategy for isolation of complete operons and genes from microbial consortia. Appl. Environ. Microbiol. 67, 89-99. doi: 10.1128/AEM.67.1.89-99.2001.
37. Faoro, H., Glogauer, A., Couto, G.H., de Souza, E.M., Rigo, L.U., Cruz, L.M., et al. (2012). Characterization of a new Acidobacteria-derived moderately thermostable lipase from a Brazilian Atlantic Forest soil metagenome. FEMS Microbiol. Ecol. 81, 386-394. doi: 10.1111/j.1574-6941.2012.01361.x.
38. Faulds, C.B. (2010). What can feruloyl esterases do for us? Phytochem. Rev. 9, 121-132. doi: 10.1007/s11101-009-9156-2.
39. Ferrer, M., Golyshina, O.V., Chernikova, T.N., Khachane, A.N., Martins Dos Santos, V.A., Yakimov, M.M., et al. (2005a). Microbial enzymes mined from the Urania deep-sea hypersaline anoxic basin. Chem. Biol. 12, 895-904. doi: 10.1016/j.chembiol.2005.05.020.
40. Ferrer, M., Golyshina, O.V., Chernikova, T.N., Khachane, A.N., Reyes-Duarte, D., Dos Santos, V., et al. (2005b). Novel hydrolase diversity retrieved from a metagenome library of bovine rumen microflora. Environ. Microbiol. 7, 1996-2010. doi: 10.1111/j.1462-2920.2005.00920.x.
41. Fischbach, M.A., and Walsh, C.T. (2009). Antibiotics for emerging pathogens. Science 325, 1089-1093. doi: 10.1126/science.1176667.
42. Forsberg, K.J., Reyes, A., Wang, B., Selleck, E.M., Sommer, M.O., and Dantas, G. (2012). The shared antibiotic resistome of soil bacteria and human pathogens. Science 337, 1107-1111. doi: 10.1126/science.1220761.
43. Fouhy, F., Ogilvie, L.A., Jones, B.V., Ross, R.P., Ryan, A.C., Dempsey, E.M., et al. (2014). Identification of aminoglycoside and beta-lactam resistance genes from within an infant gut functional metagenomic library. PLoS ONE 9:e0108016. doi: 10.1371/journal.pone.0108016.
44. Fujita, M.J., Kimura, N., Sakai, A., Ichikawa, Y., Hanyu, T., and Otsuka, M. (2011). Cloning and heterologous expression of the vibrioferrin biosynthetic gene cluster from a marine metagenomic library. Biosci. Biotechnol. Biochem. 75, 2283-2287. doi: 10.1271/bbb.110379.
45. Gibson, G.R., and Roberfroid, M.B. (1995). Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics. J. Nutr. 125, 1401-1412.
46. Gillespie, D.E., Brady, S.F., Bettermann, A.D., Cianciotto, N.P., Liles, M.R., Rondon, M.R., et al. (2002). Isolation of antibiotics turbomycin a and B from a metagenomic library of soil microbial DNA. Appl. Environ. Microbiol. 68, 4301-4306. doi: 10.1128/AEM.68.9.4301-4306.2002.
47. Guazzaroni, M.E., Morgante, V., Mirete, S., and Gonzalez-Pastor, J.E. (2013). Novel acid resistance genes from the metagenome of the Tinto River, an extremely acidic environment. Environ. Microbiol. 15, 1088-1102. doi: 10.1111/1462-2920.12021.
48. Gupta, R., Gupta, N., and Rathi, P. (2004). Bacterial lipases: an overview of production, purification and biochemical properties. Appl. Microbiol. Biotechnol. 64, 763-781. doi: 10.1007/s00253-004-1568-8.
49. Hafeez, Z., Cakir-Kiefer, C., Roux, E., Perrin, C., Mido, L., and Dary-Mourot, A. (2014). Strategies of producing bioactive peptides from milk proteins to functionalize fermented milk products. Food Res. Int. 63, 71-80. doi: 10.1016/j.foodres.2014.06.002.
50. Hamada, S., Suzuki, K., Aoki, N., and Suzuki, Y. (2013). Improvements in the qualities of gluten-free bread after using a protease obtained from Aspergillus oryzae. J. Cereal Sci. 57, 91-97. doi: 10.1016/j.jcs.2012.10.008.
51. Hao, Y., Winans, S.C., Glick, B.R., and Charles, T.C. (2010). Identification and characterization of new LuxR/LuxI-type quorum sensing systems from metagenomic libraries. Environ. Microbiol. 12, 105-117. doi: 10.1111/j.1462-2920.2009.02049.x.
52. Hasan, F., Shah, A.A., and Hameed, A. (2006). Industrial applications of microbial lipases. Enzyme Microb. Technol. 39, 235-251. doi: 10.1016/j.enzmictec.2005.10.016.
53. Hawkey, P.M. (2008). The growing burden of antimicrobial resistance. J. Antimicrob. Chemother. 62, I1-I9. doi: 10.1093/jac/dkn241.
54. Henne, A., Schmitz, R.A., Bomeke, M., Gottschalk, G., and Daniel, R. (2000). Screening of environmental DNA libraries for the presence of genes conferring lipolytic activity on Escherichia coli. Appl. Environ. Microbiol. 66, 3113-3116. doi: 10.1128/AEM.66.7.3113-3116.2000.
55. Hess, M., Sczyrba, A., Egan, R., Kim, T.W., Chokhawala, H., Schroth, G., et al. (2011). Metagenomic discovery of biomass-degrading genes and genomes from cow rumen. Science 331, 463-467. doi: 10.1126/science.1200387.
56. Hjort, K., Presti, I., Elvang, A., Marinelli, F., and Sjoling, S. (2014). Bacterial chitinase with phytopathogen control capacity from suppressive soil revealed by functional metagenomics. Appl. Microbiol. Biotechnol. 98, 2819-2828. doi: 10.1007/s00253-013-5287-x.
57. Hoessel, R., Leclerc, S., Endicott, J.A., Nobel, M.E. M., Lawrie, A., Tunnah, P., et al. (1999). Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin-dependent kinases. Nat. Cell Biol. 1, 60-67.
58. Huang, X.W., Chen, L.J., Luo, Y.B., Guo, H.Y., and Ren, F.Z. (2011). Purification, characterization, and milk coagulating properties of ginger proteases. J. Dairy Sci. 94, 2259-2269. doi: 10.3168/jds.2010-4024.
59. Iqbal, H.A., Craig, J.W., and Brady, S.F. (2014). Antibacterial enzymes from the functional screening of metagenomic libraries hosted in Ralstonia metallidurans. FEMS Microbiol. Lett. 354, 19-26. doi: 10.1111/1574-6968.12431.
60. Jayasuriya, H., Herath, K.B., Zhang, C., Zink, D.L., Basilio, A., Genilloud, O., et al. (2007). Isolation and structure of platencin: a FabH and FabF dual inhibitor with potent broad-spectrum antibiotic activity. Angew. Chem. Int. Ed Engl. 46, 4684-4688. doi: 10.1002/anie.200701058.
61. Jeon, J.H., Kim, S.J., Lee, H.S., Cha, S.S., Lee, J.H., Yoon, S.H., et al. (2011). Novel metagenome-derived carboxylesterase that hydrolyzes beta-lactam antibiotics. Appl. Environ. Microbiol. 77, 7830-7836. doi: 10.1128/AEM. 05363-11.
62. Jiang, C.J., Hao, Z.Y., Zeng, R., Shen, P.H., Li, J.F., and Wu, B. (2011). Characterization of a novel serine protease inhibitor gene from a marine metagenome. Mar. Drugs 9, 1487-1501. doi: 10.3390/md9091487.
63. Jiang, C.J., Ma, G.F., Li, S.X., Hu, T.T., Che, Z.Q., Shen, P.H., et al. (2009). Characterization of a novel beta-glucosidase-like activity from a soil metagenome. J. Microbiol. 47, 542-548. doi: 10.1007/s12275-009-0024-y.
64. Joint, F. (2001). WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria. Córdoba: Food and Agriculture Organization of the United Nations and the World Health Organization.
65. Kang, C.H., Oh, K.H., Lee, M.H., Oh, T.K., Kim, B.H., and Yoon, J. (2011). A novel family VII esterase with industrial potential from compost metagenomic library. Microb. Cell Fact. 10:41. doi: 10.1186/1475-2859-10-41.
66. Kato, K., Ono, M., and Akita, H. (1997). New total synthesis of (-)- and (+)-chuangxinmycins. Tetrahedron-Asymmetry 8, 2295-2298. doi: 10.1016/S0957-4166(97)00253-X.
67. Kay, G.L., Sergeant, M.J., Giuffra, V., Bandiera, P., Milanese, M., Bramanti, B., et al. (2014). Recovery of a medieval Brucella melitensis genome using shotgun metagenomics. MBio 5, e01337-14. doi: 10.1128/mBio.01337-14.
68. Keller, A., Horn, H., Forster, F., and Schultz, J. (2014). Computational integration of genomic traits into 16S rDNA microbiota sequencing studies. Gene 549, 186-191. doi: 10.1016/j.gene.2014.07.066.
69. Kim, Y.J., Choi, G.S., Kim, S.B., Yoon, G.S., Kim, Y.S., and Ryu, Y.W. (2006). Screening and characterization of a novel esterase from a metagenomic library. Protein Expr. Purif. 45, 315-323. doi: 10.1016/j.pep.2005.06.008.
70. Kimura, N. (2014). Metagenomic approaches to understanding phylogenetic diversity in quorum sensing. Virulence 5, 433-442. doi: 10.4161/viru.27850.
71. Lakhdari, O., Cultrone, A., Tap, J., Gloux, K., Bernard, F., Ehrlich, S.D., et al. (2010). Functional metagenomics: a high throughput screening method to decipher microbiota-driven NF-kappa B modulation in the human gut. PLoS ONE 5:e13092. doi: 10.1371/journal.pone.0013092.
72. Lane, D.J., Pace, B., Olsen, G.J., Stahl, D.A., Sogin, M.L., and Pace, N.R. (1985). Rapid-determination of 16s Ribosomal-Rna sequences for phylogenetic analyses. Proc. Natl. Acad. Sci. U.S.A. 82, 6955-6959. doi: 10.1073/pnas.82.20.6955.
73. Lang, K.S., Anderson, J.M., Schwarz, S., Williamson, L., Handelsman, J., and Singer, R.S. (2010). Novel florfenicol and chloramphenicol resistance gene discovered in Alaskan soil by using functional metagenomics. Appl. Environ. Microbiol. 76, 5321-5326. doi: 10.1128/AEM. 00323-10.
74. Langille, M.G. I., Zaneveld, J., Caporaso, J.G., McDonald, D., Knights, D., Reyes, J.A., et al. (2013). Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat. Biotechnol. 31, 814-821. doi: 10.1038/nbt.2676.
75. Lee, D.G., Jeon, J.H., Jang, M.K., Kim, N.Y., Lee, J.H., Lee, J.H., et al. (2007). Screening and characterization of a novel fibrinolytic metalloprotease from a metagenomic library. Biotechnol. Lett. 29, 465-472. doi: 10.1007/s10529-006-9263-8.
76. Lee, S.W., Won, K., Lim, H.K., Kim, J.C., Choi, G.J., and Cho, K.Y. (2004). Screening for novel lipolytic enzymes from uncultured soil microorganisms. Appl. Microbiol. Biotechnol. 65, 720-726. doi: 10.1007/s00253-004-1722-3.
77. Li, J.W., and Vederas, J.C. (2009). Drug discovery and natural products: end of an era or an endless frontier? Science 325, 161-165. doi: 10.1126/science.1168243.
78. Lim, H.K., Chung, E.J., Kim, J.C., Choi, G.J., Jang, K.S., Chung, Y.R., et al. (2005). Characterization of a forest soil metagenome clone that confers indirubin and indigo production on Escherichia coli. Appl. Environ. Microbiol. 71, 7768-7777. doi: 10.1128/AEM.71.12.7768-7777.2005.
79. Ling, L.L., Schneider, T., Peoples, A.J., Spoering, A.L., Engels, I., Conlon, B.P., et al. (2015). A new antibiotic kills pathogens without detectable resistance. Nature 517, 455-459. doi: 10.1038/nature14098.
80. Lynch, M.F., Tauxe, R.V., and Hedberg, C.W. (2009). The growing burden of foodborne outbreaks due to contaminated fresh produce: risks and opportunities. Epidemiol. Infect. 137, 307-315. doi: 10.1017/S0950268808001969.
81. Macneil, I.A., Tiong, C.L., Minor, C., August, P.R., Grossman, T.H., Loiacono, K.A., et al. (2001). Expression and isolation of antimicrobial small molecules from soil DNA libraries. J. Mol. Microbiol. Biotechnol. 3, 301-308.
82. Marko, D., Schatzle, S., Friedel, A., Genzlinger, A., Zankl, H., Meijer, L., et al. (2001). Inhibition of cyclin-dependent kinase 1 (CDK1) by indirubin derivatives in human tumour cells. Br. J. Cancer 84, 283-289. doi: 10.1054/bjoc.2000.1546.
83. Martiny, A.C., Martiny, J.B. H., Weihe, C., Field, A., and Ellis, J.C. (2011). Functional metagenomics reveals previously unrecognized diversity of antibiotic resistance genes in gulls. Front. Microbiol. 2:238. doi: 10.3389/fmicb.2011.00238.
84. McGarvey, K.M., Queitsch, K., and Fields, S. (2012). Wide variation in antibiotic resistance proteins identified by functional metagenomic screening of a soil DNA library. Appl. Environ. Microbiol. 78, 1708-1714. doi: 10.1128/AEM. 06759-11.
85. Mendes, L.W., Tsai, S.M., Navarrete, A.A., de Hollander, M., van Veen, J.A., and Kuramae, E.E. (2015). Soil-borne microbiome: linking diversity to function. Microb. Ecol. 70, 255-265. doi: 10.1007/s00248-014-0559-2.
86. Mora, L., Reig, M., and Toldra, F. (2014). Bioactive peptides generated from meat industry by-products. Food Res. Int. 65, 344-349. doi: 10.1016/j.foodres.2014.09.014.
87. Moure, A., Gullon, P., Dominguez, H., and Parajo, J.C. (2006). Advances in the manufacture, purification and applications of xylo-oligosaccharides as food additives and nutraceuticals. Process Biochem. 41, 1913-1923. doi: 10.1016/j.procbio.2006.05.011.
88. Mullany, P. (2014). Functional metagenomics for the investigation of antibiotic resistance. Virulence 5, 443-447. doi: 10.4161/viru.28196.
89. Nacke, H., Will, C., Herzog, S., Nowka, B., Engelhaupt, M., and Daniel, R. (2011). Identification of novel lipolytic genes and gene families by screening of metagenomic libraries derived from soil samples of the German Biodiversity Exploratories. FEMS Microbiol. Ecol. 78, 188-201. doi: 10.1111/j.1574-6941.2011.01088.x.
90. Nasuno, E., Kimura, N., Fujita, M.J., Nakatsu, C.H., Kamagata, Y., and Hanada, S. (2012). Phylogenetically novel LuxI/LuxR-type quorum sensing systems isolated using a metagenomic approach. Appl. Environ. Microbiol. 78, 8067-8074. doi: 10.1128/AEM. 01442-12.
91. Neveu, J., Regeard, C., and Dubow, M.S. (2011). Isolation and characterization of two serine proteases from metagenomic libraries of the Gobi and Death Valley deserts. Appl. Microbiol. Biotechnol. 91, 635-644. doi: 10.1007/s00253-011-3256-9.
92. Oh, J., Byrd, A.L., Deming, C., Conlan, S., Kong, H.H., Segre, J.A., et al. (2014). Biogeography and individuality shape function in the human skin metagenome. Nature 514, 59-64. doi: 10.1038/nature13786.
93. Ouyang, L.M., Liu, J.Y., Qiao, M., and Xu, J.H. (2013). Isolation and biochemical characterization of two novel metagenome-derived esterases. Appl. Biochem. Biotechnol. 169, 15-28. doi: 10.1007/s12010-012-9949-4.
94. Palackal, N., Lyon, C.S., Zaidi, S., Luginbuhl, P., Dupree, P., Goubet, F., et al. (2007). A multifunctional hybrid glycosyl hydrolase discovered in an uncultured microbial consortium from ruminant gut. Appl. Microbiol. Biotechnol. 74, 113-124. doi: 10.1007/s00253-006-0645-6.
95. Pallecchi, L., Bartoloni, A., Paradisi, F., and Rossolini, G.M. (2008). Antibiotic resistance in the absence of antimicrobial use: mechanisms and implications. Expert Rev. Anti Infect. Ther. 6, 725-732. doi: 10.1586/14787210.6.5.725.
96. Panda, T., and Gowrishankar, B.S. (2005). Production and applications of esterases. Appl. Microbiol. Biotechnol. 67, 160-169. doi: 10.1007/s00253-004-1840-y.
97. Panesar, P.S., Kumari, S., and Panesar, R. (2010). Potential applications of immobilized beta-galactosidase in food processing industries. Enzyme Res. 2010:473137. doi: 10.4061/2010/473137.
98. Parsley, L.C., Consuegra, E.J., Kakirde, K.S., Land, A.M., Harper, W.F. Jr., and Liles, M.R. (2010). Identification of diverse antimicrobial resistance determinants carried on bacterial, plasmid, or viral metagenomes from an activated sludge microbial assemblage. Appl. Environ. Microbiol. 76, 3753-3757. doi: 10.1128/AEM. 03080-09.
99. Peng, Q., Wang, X., Shang, M., Huang, J., Guan, G., Li, Y., et al. (2014). Isolation of a novel alkaline-stable lipase from a metagenomic library and its specific application for milkfat flavor production. Microb. Cell Fact. 13:1. doi: 10.1186/1475-2859-13-1.
100. Piel, J. (2002). A polyketide synthase-peptide synthetase gene cluster from an uncultured bacterial symbiont of Paederus beetles. Proc. Natl. Acad. Sci. U.S.A. 99, 14002-14007. doi: 10.1073/pnas.222481399.
101. Pooja, S., Pushpanathan, M., Jayashree, S., Gunasekaran, P., and Rajendhran, J. (2015). Identification of periplasmic alpha-amlyase from cow dung metagenome by product induced gene expression profiling (Pigex). Indian J. Microbiol. 55, 57-65. doi: 10.1007/s12088-014-0487-3.
102. Pushpam, P.L., Rajesh, T., and Gunasekaran, P. (2011). Identification and characterization of alkaline serine protease from goat skin surface metagenome. AMB Express 1:3. doi: 10.1186/2191-0855-1-3.
103. Rabausch, U., Juergensen, J., Ilmberger, N., Bohnke, S., Fischer, S., Schubach, B., et al. (2013). Functional screening of metagenome and genome libraries for detection of novel flavonoid-modifying enzymes. Appl. Environ. Microbiol. 79, 4551-4563. doi: 10.1128/AEM. 01077-13.
104. Rhee, J.K., Ahn, D.G., Kim, Y.G., and Oh, J.W. (2005). New thermophilic and thermostable esterase with sequence similarity to the hormone-sensitive lipase family, cloned from a metagenomic library. Appl. Environ. Microbiol. 71, 817-825. doi: 10.1128/AEM.71.2.817-825.2005.
105. Riaz, K., Elmerich, C., Moreira, D., Raffoux, A., Dessaux, Y., and Faure, D. (2008). A metagenomic analysis of soil bacteria extends the diversity of quorum-quenching lactonases. Environ. Microbiol. 10, 560-570. doi: 10.1111/j.1462-2920.2007.01475.x.
106. Richardson, T.H., Tan, X.Q., Frey, G., Callen, W., Cabell, M., Lam, D., et al. (2002). A novel, high performance enzyme for starch liquefaction - Discovery and optimization of a low pH, thermostable alpha-amylase. J. Biol. Chem. 277, 26501-26507. doi: 10.1074/jbc.M203183200.
107. Robertson, D.E., Chaplin, J.A., Desantis, G., Podar, M., Madden, M., Chi, E., et al. (2004). Exploring nitrilase sequence space for enantioselective catalysis. Appl. Environ. Microbiol. 70, 2429-2436. doi: 10.1128/AEM.70.4.2429-2436.2004.
108. Rondon, M.R., August, P.R., Bettermann, A.D., Brady, S.F., Grossman, T.H., Liles, M.R., et al. (2000). Cloning the soil metagenome: a strategy for accessing the genetic and functional diversity of uncultured microorganisms. Appl. Environ. Microbiol. 66, 2541-2547. doi: 10.1128/AEM.66.6.2541-2547.2000.
109. Rosario, K., and Breitbart, M. (2011). Exploring the viral world through metagenomics. Curr. Opin. Virol. 1, 289-297. doi: 10.1016/j.coviro.2011.06.004.
110. Sariozlu, N.Y., and Kivanc, M. (2009). Isolation of gallic acid-producing microorganisms and their use in the production of gallic acid from gall nuts and sumac. Afr. J. Biotechnol. 8, 1110-1115.
111. Scanlon, T.C., Dostal, S.M., and Griswold, K.E.;1. (2014). A high-throughput screen for antibiotic drug discovery. Biotechnol. Bioeng. 111, 232-243. doi: 10.1002/bit.25019.
112. Schipper, C., Hornung, C., Bijtenhoorn, P., Quitschau, M., Grond, S., and Streit, W.R. (2009). Metagenome-derived clones encoding two novel lactonase family proteins involved in biofilm inhibition in Pseudomonas aeruginosa. Appl. Environ. Microbiol. 75, 224-233. doi: 10.1128/AEM. 01389-08.
113. Schirmer, A., Gadkari, R., Reeves, C.D., Ibrahim, F., Delong, E.F., and Hutchinson, C.R. (2005). Metagenomic analysis reveals diverse polyketide synthase gene clusters in microorganisms associated with the marine sponge Discodermia dissoluta. Appl. Environ. Microbiol. 71, 4840-4849. doi: 10.1128/AEM.71.8.4840-4849.2005.
114. Schoch, C.L., Seifert, K.A., Huhndorf, S., Robert, V., Spouge, J.L., Levesque, C.A., et al. (2012). Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi. Proc. Natl. Acad. Sci. U.S.A. 109, 6241-6246. doi: 10.1073/pnas.1117018109.
115. Shen, D., Xu, J.H., Wu, H.Y., and Liu, Y.Y. (2002). Significantly improved esterase activity of Trichosporon brassicae cells for ketoprofen resolution by 2-propanol treatment. J. Mol. Catal. B Enzym. 18, 219-224. doi: 10.1016/S1381-1177(02)00099-1.
116. Smits, S.L., and Osterhaus, A.D. (2013). Virus discovery: one step beyond. Curr. Opin. Virol. 3, e1-e6. doi: 10.1016/j.coviro.2013.03.007.
117. Sommer, M.O. A., Dantas, G., and Church, G.M. (2009). Functional characterization of the antibiotic resistance reservoir in the human microflora. Science 325, 1128-1131. doi: 10.1126/science.1176950.
118. Staley, C., Johnson, D., Gould, T.J., Wang, P., Phillips, J., Cotner, J.B., et al. (2015). Frequencies of heavy metal resistance are associated with land cover type in the Upper Mississippi River. Sci. Total Environ. 511, 461-468. doi: 10.1016/j.scitotenv.2014.12.069.
119. Staley, J.T., and Konopka, A. (1985). Measurement of insitu activities of nonphotosynthetic microorganisms in aquatic and terrestrial habitats. Annu. Rev. Microbiol. 39, 321-346. doi: 10.1146/annurev.mi.39.100185.001541.
120. Streit, W.R., and Entcheva, P. (2003). Biotin in microbes, the genes involved in its biosynthesis, its biochemical role and perspectives for biotechnological production. Appl. Microbiol. Biotechnol. 61, 21-31. doi: 10.1007/s00253-002-1186-2.
121. Streit, W.R., and Schmitz, R.A. (2004). Metagenomics - the key to the uncultured microbes. Curr. Opin. Microbiol. 7, 492-498. doi: 10.1016/j.mib.2004.08.002.
122. Su, J.Q., Wei, B., Xu, C.Y., Qiao, M., and Zhu, Y.G. (2014). Functional metagenomic characterization of antibiotic resistance genes in agricultural soils from China. Environ. Int. 65, 9-15. doi: 10.1016/j.envint.2013.12.010.
123. Tannieres, M., Beury-Cirou, A., Vigouroux, A., Mondy, S., Pellissier, F., Dessaux, Y., et al. (2013). A metagenomic study highlights phylogenetic proximity of quorum-quenching and xenobiotic-degrading amidases of the AS-family. PLoS ONE 8:e65473. doi: 10.1371/journal.pone.0065473.
124. Tao, W., Lee, M.H., Wu, J., Kim, N.H., Kim, J.C., Chung, E., et al. (2012). Inactivation of chloramphenicol and florfenicol by a novel chloramphenicol hydrolase. Appl. Environ. Microbiol. 78, 6295-6301. doi: 10.1128/AEM. 01154-12.
125. Torsvik, V., Goksoyr, J., and Daae, F.L. (1990). High diversity in DNA of soil bacteria. Appl. Environ. Microbiol. 56, 782-787.
126. Uchiyama, T., Abe, T., Ikemura, T., and Watanabe, K. (2005). Substrate-induced gene-expression screening of environmental metagenome libraries for isolation of catabolic genes. Nat. Biotechnol. 23, 88-93. doi: 10.1038/nbt1048.
127. Uchiyama, T., and Miyazaki, K. (2009). Functional metagenomics for enzyme discovery: challenges to efficient screening. Curr. Opin. Biotechnol. 20, 616-622. doi: 10.1016/j.copbio.2009.09.010.
128. Uchiyama, T., and Miyazaki, K. (2010). Product-induced gene expression, a product-responsive reporter assay used to screen metagenomic libraries for enzyme-encoding genes. Appl. Environ. Microbiol. 76, 7029-7035. doi: 10.1128/AEM. 00464-10.
129. Uchiyama, T., and Watanabe, K. (2006). Improved inverse PCR scheme for metagenome walking. Biotechniques 41, 183-188. doi: 10.2144/000112210.
130. van der Maarel, M.J., van der Veen, B., Uitdehaag, J.C., Leemhuis, H., and Dijkhuizen, L. (2002). Properties and applications of starch-converting enzymes of the alpha-amylase family. J. Biotechnol. 94, 137-155. doi: 10.1016/S0168-1656(01)00407-2.
131. Venter, J.C., Remington, K., Heidelberg, J.F., Halpern, A.L., Rusch, D., Eisen, J.A., et al. (2004). Environmental genome shotgun sequencing of the Sargasso Sea. Science 304, 66-74. doi: 10.1126/science.1093857.
132. Ververidis, F., Trantas, E., Douglas, C., Vollmer, G., Kretzschmar, G., and Panopoulos, N. (2007a). Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part I: Chemical diversity, impacts on plant biology and human health. Biotechnol. J. 2, 1214-1234. doi: 10.1002/biot.200700084.
133. Ververidis, F., Trantas, E., Douglas, C., Vollmer, G., Kretzschmar, G., and Panopoulos, N. (2007b). Biotechnology of flavonoids and other phenylpropanoid-derived natural products. Part II: Reconstruction of multienzyme pathways in plants and microbes. Biotechnol. J. 2, 1235-1249. doi: 10.1002/biot.200700184.
134. Vester, J.K., Glaring, M.A., and Stougaard, P. (2014). Discovery of novel enzymes with industrial potential from a cold and alkaline environment by a combination of functional metagenomics and culturing. Microb. Cell Fact. 13:72. doi: 10.1186/1475-2859-13-72.
135. Voget, S., Leggewie, C., Uesbeck, A., Raasch, C., Jaeger, K.E., and Streit, W.R. (2003). Prospecting for novel biocatalysts in a soil metagenome. Appl. Environ. Microbiol. 69, 6235-6242. doi: 10.1128/AEM.69.10.6235-6242.2003.
136. Von Wettstein, D., Mikhaylenko, G., Froseth, J.A., and Kannangara, C.G. (2000). Improved barley broiler feed with transgenic malt containing heat-stable (1,3-1,4)-beta-glucanase. Proc. Natl. Acad. Sci. U.S.A. 97, 13512-13517. doi: 10.1073/pnas.97.25.13512.
137. Walter, J., Mangold, M., and Tannock, G.W. (2005). Construction, analysis, and beta-glucanase screening of a bacterial artificial chromosome library from the large-bowel microbiota of mice. Appl. Environ. Microbiol. 71, 2347-2354. doi: 10.1128/AEM.71.5.2347-2354.2005.
138. Wang, K., Li, G., Yu, S.Q., Zhang, C.T., and Liu, Y.H. (2010). A novel metagenome-derived beta-galactosidase: gene cloning, overexpression, purification and characterization. Appl. Microbiol. Biotechnol. 88, 155-165. doi: 10.1007/s00253-010-2744-7.
139. Wang, K., Lu, Y., Liang, W.Q., Wang, S.D., Jiang, Y., Huang, R., et al. (2012). Enzymatic synthesis of galacto-oligosaccharides in an organic-aqueous biphasic system by a novel beta-galactosidase from a metagenomic library. J. Agric. Food Chem. 60, 3940-3946. doi: 10.1021/jf300890d.
140. Warnecke, F., Luginbuhl, P., Ivanova, N., Ghassemian, M., Richardson, T.H., Stege, J.T., et al. (2007). Metagenomic and functional analysis of hindgut microbiota of a wood-feeding higher termite. Nature 450, 560-565. doi: 10.1038/nature06269.
141. Wendel, A.M., Johnson, D.H., Sharapov, U., Grant, J., Archer, J.R., Monson, T., et al. (2009). Multistate Outbreak of Escherichia coli O157:H7 Infection associated with consumption of packaged spinach, August-September 2006: the wisconsin investigation. Clin. Infect. Dis. 48, 1079-1086. doi: 10.1086/597399.
142. World Health Organization. (2014). Antimicrobial Resistance: Global Report On Surveillance. Geneva: World Health Organization.
143. Wu, D., and Bird, M.R. (2010). The interaction of protein and polyphenol species in ready to drink black tea liquor production. J. Food Process Eng. 33, 481-505. doi: 10.1111/j.1745-4530.2008.00286.x.
144. Yao, J., Chen, Q., Zhong, G., Cao, W., Yu, A., and Liu, Y. (2014). Immobilization and characterization of tannase from a metagenomic library and its use for removal of tannins from green tea infusion. J. Microbiol. Biotechnol. 24, 80-86. doi: 10.4014/jmb.1308.08047.
145. Yao, J., Fan, X.J., Lu, Y., and Liu, Y.H. (2011). Isolation and characterization of a novel tannase from a metagenomic library. J. Agric. Food Chem. 59, 3812-3818. doi: 10.1021/jf104394m.
146. Yun, J., and Ryu, S. (2005). Screening for novel enzymes from metagenome and SIGEX, as a way to improve it. Microb. Cell Fact. 4:8. doi: 10.1186/1475-2859-4-8.
147. Zhu, B., and Panek, J.S. (2001). Methodology based on chiral silanes in the synthesis of polypropionate-derived natural products - Total synthesis of epothilone A. Eur. J. Org. Chem. 2001, 1701-1714. doi: 10.1002/1099-0690(200105)2001:9<1701::AID-EJOC1701>3.0.CO;2-#.