High-throughput strategies for the discovery and engineering of enzymes for biocatalysis

Bioprocess and Biosystems Engineering

Volumn 40, Issue 2, 2017, Pages 161-180

  Jacques, Philippe ^a   Béchet, Max ^a   Bigan, Muriel ^a   Caly, Delphine ^a   Chataigné, Gabrielle ^a   Coutte, François ^a   Flahaut, Christophe ^a   Heuson, Egon ^a   Leclère, Valérie ^a   Lecouturier, Didier ^a   Phalip, Vincent ^a   Ravallec, Rozenn ^a   Dhulster, Pascal ^a   Froidevaux, Rénato ^a  

^a UNIV LILLE   (France)

Author keywords

Biotechnologies; Characterization; Enzyme catalysis; High throughput screening

Indexed keywords

BIOTECHNOLOGY; CATALYSIS; CELL CULTURE; CELL ENGINEERING; CHEMICAL INDUSTRY; DRUG PRODUCTS; MASS SPECTROMETRY; MOLECULAR BIOLOGY; THROUGHPUT;

BIOINFORMATICS TOOLS; ENZYME CATALYSIS; HIGH THROUGHPUT SCREENING; HIGH THROUGHPUT SCREENING METHODS; MOLECULAR BIOLOGY TOOLS; MUTANT LIBRARIES; TECHNOLOGICAL INNOVATION; TOOLS AND TECHNOLOGIES;

ENZYMES;

ENZYME; MICROBIAL ENZYME;

BIOCATALYSIS; BIOCATALYST; BIOPROCESS; BIOREACTOR; ENZYME PURIFICATION; EXPERIMENTAL DESIGN; GENETIC VARIABILITY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HIGH THROUGHPUT SCREENING; MASS SPECTROMETRY; MATRIX ASSISTED LASER DESORPTION IONIZATION TIME OF FLIGHT MASS SPECTROMETRY; METAGENOMICS; MICROFLUIDICS; MUTAGENESIS; NONHUMAN; PRIORITY JOURNAL; PROCESS OPTIMIZATION; REVIEW; BIOSYNTHESIS; CATALYSIS; CHEMISTRY; GENETICS; PROCEDURES; PROTEIN ENGINEERING;

CATALYSIS; ENZYMES; PROTEIN ENGINEERING;

EID: 84991073144     PISSN: 16157591     EISSN: 16157605     Source Type: Journal    
DOI: 10.1007/s00449-016-1690-x     Document Type: Review

References (186)

1. Singhania RR, Patel AK, Thomas L et al (2015) Industrial enzymes. In: Pandey A, Höfer R, Taherzadeh M et al (eds) Industrial biorefineries & white biotechnology. Elsevier, London, pp 473–497
2. Damborsky J, Brezovsky J (2013) ScienceDirect computational tools for designing and engineering enzymes. Curr Opin Chem Biol 19:8–16. doi:10.1016/j.cbpa.2013.12.003
3. Heux S, Donohue MJO, Dumon C (2015) White biotechnology: state of the art strategies for the development of biocatalysts for biore fi ning. Biotechnol Adv 33:1653–1670. doi:10.1016/j.biotechadv.2015.08.004
4. Tiwari MK, Singh R, Singh RK et al (2012) Computational approaches for rational design of proteins with novel functionalities structural, catalytic, sensory, and regulatory functions. Rational design of enzymes is a great challenge to our understanding of design or engineer proteins that fold. Comput Struct Biotechnol 2:1–13. doi:10.5936/csbj.201209002
5. Wölcke J, Ullmann D (2001) Miniaturized HTS technologies—uHTS. Drug Discov Today 6:637–646. doi:10.1016/S1359-6446(01)01807-4
6. Cacho RA, Tang Y, Chooi Y-H (2015) Next-generation sequencing approach for connecting secondary metabolites to biosynthetic gene clusters in fungi. Frontiers Microbiol 5:774. doi:10.3389/fmicb.2014.00774
7. Weber T, Kim HU (2016) The secondary metabolite bioinformatics portal: computational tools to facilitate synthetic biology of secondary metabolite production. Synth Syst Biotechnol. doi:10.1016/j.synbio.2015.12.002
8. Medema MH, Kottmann R, Yilmaz P et al (2015) The minimum information about a biosynthetic gene cluster (MIBiG) specification. Nat Chem Biol 11:625–631. doi:10.1038/nchembio.1890
9. Caradec T, Pupin M, Vanvlassenbroeck A et al (2014) Prediction of monomer isomery in florine: a workflow dedicated to nonribosomal peptide discovery. PLoS One. doi:10.1371/journal.pone.0085667
10. Leclère V, Weber T, Jacques P, Pupin M (2016) Bioinformatics tools for the discovery of new nonribosomal peptides. Methods in molecular biology (Clifton, NJ) 1401:209–232. doi:10.1007/978-1-4939-3375-4_14
11. Flissi A, Dufresne Y, Michalik J et al (2015) Norine, the knowledgebase dedicated to non-ribosomal peptides, is now open to crowdsourcing. Nucleic Acids Res 44:D1113–D1118. doi:10.1093/nar/gkv1143
12. Conway KR, Boddy CN (2013) ClusterMine360: a database of microbial PKS/NRPS biosynthesis. Nucleic Acids Res 41:402–407. doi:10.1093/nar/gks993
13. Pupin M, Esmaeel Q, Flissi A et al (2015) Norine: a powerful resource for novel nonribosomal peptide discovery. Synth Syst Biotechnol. doi:10.1016/j.synbio.2015.11.001
14. Weber T, Blin K, Duddela S et al (2015) AntiSMASH 3. 0—a comprehensive resource for the genome mining of biosynthetic gene clusters. 43:237–243. doi:10.1093/nar/gkv437
15. Starcevic A, Zucko J, Simunkovic J et al (2008) ClustScan: an integrated program package for the semi-automatic annotation of modular biosynthetic gene clusters and in silico prediction of novel chemical structures. Nucleic Acids Res 36:6882–6892. doi:10.1093/nar/gkn685
16. Khaldi N, Seifuddin FT, Turner G et al (2010) SMURF: genomic mapping of fungal secondary metabolite clusters. Fungal Genet Biol 47:736–741. doi:10.1016/j.fgb.2010.06.003
17. Esmaeel Q, Pupin M, Kieu NP et al (2016) Burkholderia genome mining for nonribosomal peptide synthetases reveals a great potential for novel siderophores and lipopeptides synthesis. MicrobiologyOpen. doi:10.1002/mbo3.347
18. Rohe P, Venkanna D, Kleine B et al (2012) An automated workflow for enhancing microbial bioprocess optimization on a novel microbioreactor platform. Microb Cell Fact 11:144. doi:10.1186/1475-2859-11-144
19. Zhao J, Li Y, Zhang C et al (2012) Genome shuffling of Bacillus amyloliquefaciens for improving antimicrobial lipopeptide production and an analysis of relative gene expression using FQ RT-PCR. J Ind Microbiol Biotechnol 39:889–896. doi:10.1007/s10295-012-1098-9
20. Mali P, Yang L, Esvelt KM et al (2013) RNA-guided human genome engineering via Cas9. Science 339:823–826. doi:10.1126/science.1232033
21. Le Cong F, Ran A, Cox D et al (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339:819–823. doi:10.1126/science.1231143
22. Mei Y, Wang Y, Chen H et al (2016) Recent progress in CRISPR/Cas9 technology. J Genet Genomics 43:63–75. doi:10.1016/j.jgg.2016.01.001
23. Kanaar R, Wyman C, Rothstein R (2008) Quality control of DNA break metabolism: in the “end”, it’s a good thing. EMBO J 27:581–588. doi:10.1038/emboj.2008.11
24. Jiang W, Bikard D, Cox D et al (2013) RNA-guided editing of bacterial genomes using CRISPR–Cas systems. Nat Biotechnol 31:233–239. doi:10.1038/nbt.2508
25. Cobb RE, Wang Y, Zhao H (2014) High-efficiency multiplex genome editing of Streptomyces species using an engineered CRISPR/Cas system. ACS Synth Biol. doi:10.1021/sb500351f
26. Tong Y, Charusanti P, Zhang L et al (2015) CRISPR–Cas9 based engineering of actinomycetal genomes. ACS Synth Biol 4:1020–1029. doi:10.1021/acssynbio.5b00038
27. Hodgkins A, Farne A, Perera S et al (2015) WGE: a CRISPR database for genome engineering. Bioinformatics 31:3078–3080. doi:10.1093/bioinformatics/btv308
28. Xu H, Xiao T, Chen CH et al (2015) Sequence determinants of improved CRISPR sgRNA design. Genome Res 25:1147–1157. doi:10.1101/gr.191452.115
29. Blin K, Pedersen LE, Weber T, Lee SY (2016) CRISPy-web: an online resource to design sgRNAs for CRISPR applications. Synth Syst Biotechnol. doi:10.1016/j.synbio.2016.01.003
30. Weber T, Blin K, Duddela S et al (2015) AntiSMASH 3.0—a comprehensive resource for the genome mining of biosynthetic gene clusters. Nucleic Acids Res 43:1–7. doi:10.1093/nar/gkv437
31. Bikard D, Euler CW, Jiang W et al (2014) Exploiting CRISPR–Cas nucleases to produce sequence-specific antimicrobials. Nat Biotechnol 32:1146–1150. doi:10.1038/nbt.3043
32. Citorik RJ, Mimee M, Lu TK (2014) Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases. Nat Biotechnol 32:1141–1145. doi:10.1038/nbt.3011
33. Beisel CL, Gomaa AA, Barrangou R (2014) A CRISPR design for next-generation antimicrobials. Genome Biol 15:516. doi:10.1186/s13059-014-0516-x
34. Peng J, Zhou Y, Zhu S, Wei W (2015) High-throughput screens in mammalian cells using the CRISPR–Cas9 system. FEBS J 282:2089–2096. doi:10.1111/febs.13251
35. Shi J, Wang E, Milazzo JP et al (2015) Discovery of cancer drug targets by CRISPR–Cas9 screening of protein domains. Nat Biotechnol 33:1–10. doi:10.1038/nbt.3235
36. Kilian KA, Moghe PV (2016) High throughput strategies for the design, discovery, and analysis of biomaterials. Acta Biomater 34:v–vi. doi:10.1016/j.actbio.2016.03.019
37. Bertin PN, Heinrich-Salmeron A, Pelletier E et al (2011) Metabolic diversity among main microorganisms inside an arsenic-rich ecosystem revealed by meta- and proteo-genomics. ISME J 5:1735–1747. doi:10.1038/ismej.2011.51
38. Piel J (2002) A polyketide synthase-peptide synthetase gene cluster from an uncultured bacterial symbiont of Paederus beetles. Proc Natl Acad Sci USA 99:14002–14007. doi:10.1073/pnas.222481399
39. Wierzbicka-Woś A, Bartasun P, Cieśliński H et al (2013) Cloning and characterization of a novel cold-active glycoside hydrolase family 1 enzyme with β-glucosidase, β-fucosidase and β-galactosidase activities. BMC Biotechnol 13:22. doi:10.1186/1472-6750-13-22
40. Schröder C, Elleuche S, Blank S, Antranikian G (2014) Characterization of a heat-active archaeal β-glucosidase from a hydrothermal spring metagenome. Enzyme Microb Technol 57:48–54. doi:10.1016/j.enzmictec.2014.01.010
41. Zhu Y, Li J, Cai H et al (2013) Characterization of a new and thermostable esterase from a metagenomic library. Microbiol Res 168:589–597. doi:10.1016/j.micres.2013.04.004
42. Harris AD (2012) Soil metagenomics: a prospective approach for novel enzyme discovery. Int J Curr Res 4:88–92
43. Hawksworth DL (1991) The fungal dimension of biodiversity: magnitude, significance, and conservation. Mycol Res 95:641–655. doi:10.1016/S0953-7562(09)80810-1
44. Blackwell M (2011) The fungi: 1, 2, 3… 5.1 million species? Am J Bot 98:426–438. doi:10.3732/ajb.1000298
45. Reeder J, Knight R (2009) The “rare biosphere”: a reality check. Nat Methods 6:636–637. doi:10.1038/nmeth0909-636
46. Ling LL, Schneider T, Peoples AJ et al (2015) A new antibiotic kills pathogens without detectable resistance. Nature 517:455–459. doi:10.1038/nature14098
47. Lewis K, Epstein S, D’Onofrio A, Ling LL (2010) Uncultured microorganisms as a source of secondary metabolites. J Antibiot 63:468–476. doi:10.1038/ja.2010.87
48. Wohlgemuth R, Plazl I, Žnidaršič-Plazl P et al (2015) Microscale technology and biocatalytic processes: opportunities and challenges for synthesis. Trends Biotechnol 33:302–314. doi:10.1016/j.tibtech.2015.02.010
49. Tušek A, Šalić A, Kurtanjek Ž, Zelić B (2012) Modeling and kinetic parameter estimation of alcohol dehydrogenase-catalyzed hexanol oxidation in a microreactor. Eng Life Sci 12:49–56. doi:10.1002/elsc.201100020
50. Žnidaršič Plazl P (2014) Enzymatic microreactors utilizing non-aqueous media. Chim Oggi/Chem Today 32:54–60
51. Kintses B, Hein C, Mohamed MF et al (2012) Picoliter cell lysate assays in microfluidic droplet compartments for directed enzyme evolution. Chem Biol 19:1001–1009. doi:10.1016/j.chembiol.2012.06.009
52. Wójcik M, Telzerow A, Quax WJ, Boersma YL (2015) High-throughput screening in protein engineering: recent advances and future perspectives. Int J Mol Sci 16:24918–24945. doi:10.3390/ijms161024918
53. Boersma YL, Dröge MJ, Quax WJ (2007) Selection strategies for improved biocatalysts. FEBS J 274:2181–2195. doi:10.1111/j.1742-4658.2007.05782.x
54. Pitzler C, Wirtz G, Vojcic L et al (2014) A fluorescent hydrogel-based flow cytometry high-throughput screening platform for hydrolytic enzymes. Chem Biol 21:1733–1742. doi:10.1016/j.chembiol.2014.10.018
55. Tu R, Martinez R, Prodanovic R et al (2011) A flow cytometry-based screening system for directed evolution of proteases. J Biomol Screen 16:285–294. doi:10.1177/1087057110396361
56. Becker S, Höbenreich H, Vogel A et al (2008) Single-cell high-throughput screening to identify enantioselective hydrolytic enzymes. Angew Chem Int Ed 47:5085–5088. doi:10.1002/anie.200705236
57. Fernández-Álvaro E, Snajdrova R, Jochens H et al (2011) A combination of in vivo selection and cell sorting for the identification of enantioselective biocatalysts. Angew Chem Int Ed 50:8584–8587. doi:10.1002/anie.201102360
58. Davids T, Schmidt M, Böttcher D, Bornscheuer UT (2013) Strategies for the discovery and engineering of enzymes for biocatalysis. Curr Opin Chem Biol 17:215–220. doi:10.1016/j.cbpa.2013.02.022
59. Yoo TH, Pogson M, Iverson BL, Georgiou G (2012) Directed evolution of highly selective proteases by using a novel FACS-based screen that capitalizes on the p53 regulator MDM2. ChemBioChem 13:649–653. doi:10.1002/cbic.201100718
60. Agresti JJ, Antipov E, Abate AR et al (2010) Ultrahigh-throughput screening in drop-based microfluidics for directed evolution. Proc Natl Acad Sci USA 107:4004–4009. doi:10.1073/pnas.0910781107
61. Deal KS, Easley CJ (2012) Self-regulated, droplet-based sample chopper for microfluidic absorbance detection. Anal Chem 84:1510–1516. doi:10.1021/ac202791d
62. Cecchini MP, Hong J, Lim C et al (2011) Ultrafast surface enhanced resonance raman scattering detection in droplet-based microfluidic systems. Anal Chem 83:3076–3081. doi:10.1021/ac103329b
63. Lee SA, Zheng G, Mukherjee N, Yang C (2012) On-chip continuous monitoring of motile microorganisms on an ePetri platform. Lab Chip 12:2385–2390. doi:10.1039/C2LC40090A
64. Salisbury CM, Maly DJ, Ellman JA (2002) Peptide microarrays for the determination of protease substrate specificity. J Am Chem Soc 124:14868–14870. doi:10.1021/ja027477q
65. Zhu Q, Uttamchandani M, Li D et al (2003) Enzymatic profiling system in a small-molecule microarray. Org Lett 5:1257–1260. doi:10.1021/ol034233h
66. Houseman BT, Mrksich M (2002) Carbohydrate arrays for the evaluation of protein binding and enzyme activity. Chem Biol 9:443–454
67. Yeo WS, Mrksich M (2003) Self-assembled monolayers that transduce enzymatic activities to electrical signals. Angew Chem Int Ed 42:3121–3124. doi:10.1002/anie.200250862
68. Gosalia DN, Diamond SL (2003) Printing chemical libraries on microarrays for fluid phase nanoliter reactions. Proc Natl Acad Sci USA 100:8721–8726. doi:10.1073/pnas.1530261100
69. Park CB, Clark DS (2002) Sol-gel encapsulated enzyme arrays for high-throughput screening of biocatalytic activity. Biotechnol Bioeng 78:229–235. doi:10.1002/bit.10238
70. Bisswanger H (2014) Enzyme assays. Perspectives. Science 1:41–55. doi:10.1016/j.pisc.2014.02.005
71. Haswell SJ, Middleton RJ, O’Sullivan B et al (2001) The application of micro reactors to synthetic chemistry. Chem Commun 80:391–398. doi:10.1039/b008496o
72. Abbas A, Treizebre A, Supiot P et al (2009) Cold plasma functionalized TeraHertz BioMEMS for enzyme reaction analysis. Biosens Bioelectron 25:154–160. doi:10.1016/j.bios.2009.06.029
73. Kim DN, Lee Y, Koh W-G (2009) Fabrication of microfluidic devices incorporating bead-based reaction and microarray-based detection system for enzymatic assay. Sens Actuat B Chem 137:305–312. doi:10.1016/j.snb.2008.12.042
74. Draper MC, Niu X, Cho S et al (2012) Compartmentalization of electrophoretically separated analytes in a multiphase microfluidic platform. Anal Chem 84:5801–5808. doi:10.1021/ac301141x
75. DeMello AJ (2006) Control and detection of chemical reactions in microfluidic systems. Nature 442:394–402. doi:10.1038/nature05062
76. Elagli A, Laurette S, Treizebre A et al (2014) Diffusion based kinetic selectivity modulation of enzymatic proteolysis in a microfluidic reactor: experimental analysis and stochastic modeling. RSC Adv 4:3873–3882. doi:10.1039/C3RA46005C
77. Honda T, Miyazaki M, Nakamura H, Maeda H (2006) Facile preparation of an enzyme-immobilized microreactor using a cross-linking enzyme membrane on a microchannel surface. Adv Synth Catal 348:2163–2171. doi:10.1002/adsc.200606224
78. Song YS, Shin HY, Lee JY et al (2012) β-Galactosidase-immobilised microreactor fabricated using a novel technique for enzyme immobilisation and its application for continuous synthesis of lactulose. Food Chem 133:611–617. doi:10.1016/j.foodchem.2012.01.096
79. Anuar ST, Zhao Y-Y, Mugo SM, Curtis JM (2013) The development of a capillary microreactor for transesterification reactions using lipase immobilized onto a silica monolith. J Mol Catal B Enzym 92:62–70. doi:10.1016/j.molcatb.2013.03.013
80. Ogończyk D, Jankowski P, Garstecki P et al (2012) Functionalization of polycarbonate with proteins; open-tubular enzymatic microreactors. Lab Chip 12:2743. doi:10.1039/c2lc40204a
81. Laurette S, Treizebre A, Elagli A et al (2012) Highly sensitive terahertz spectroscopy in microsystem. RSC Adv 2:10064. doi:10.1039/c2ra21320f
82. Elagli A, Belhacene K, Vivien C et al (2014) Facile immobilization of enzyme by entrapment using a plasma-deposited organosilicon thin film. J Mol Catal B Enzym 110:77–86. doi:10.1016/j.molcatb.2014.09.014
83. Büchs J (2001) Introduction to advantages and problems of shaken cultures. Biochem Eng J 7:91–98. doi:10.1016/S1369-703X(00)00106-6
84. Lattermann C, Büchs J (2015) Microscale and miniscale fermentation and screening. Curr Opin Biotechnol 35:1–6. doi:10.1016/j.copbio.2014.12.005
85. Bhambure R, Kumar K, Rathore AS (2011) High-throughput process development for biopharmaceutical drug substances. Trends Biotechnol 29:127–135. doi:10.1016/j.tibtech.2010.12.001
86. Marques M, Cabral J, Fernandes P (2009) High throughput in biotechnology: from shake-flasks to fully instrumented microfermentors. Recent Pat Biotechnol 3:124–140. doi:10.2174/187220809788700193
87. Käß F, Prasad A, Tillack J et al (2014) Rapid assessment of oxygen transfer impact for Corynebacterium glutamicum. Bioprocess Biosyst Eng. doi:10.1007/s00449-014-1234-1
88. Duetz WA (2007) Microtiter plates as mini-bioreactors: miniaturization of fermentation methods. Trends Microbiol 15:469–475. doi:10.1016/j.tim.2007.09.004
89. Huber R, Roth S, Rahmen N, Büchs J (2011) Utilizing high-throughput experimentation to enhance specific productivity of an E. coli T7 expression system by phosphate limitation. BMC Biotechnol 11:22. doi:10.1186/1472-6750-11-22
90. Sundstrom ER, Criddle CS (2015) Optimization of methanotrophic growth and production of poly(3-hydroxybutyrate) in a high-throughput microbioreactor system. Appl Environ Microbiol 81:4767–4773. doi:10.1128/aem.00025-15
91. Huber R, Ritter D, Hering T et al (2009) Robo-Lector—a novel platform for automated high-throughput cultivations in microtiter plates with high information content. Microb Cell Fact 8:42. doi:10.1186/1475-2859-8-42
92. Huber R, Wulfhorst H, Maksym L et al (2011) Screening for enzyme activity in turbid suspensions with scattered light. Biotechnol Prog 27:555–561. doi:10.1002/btpr.519
93. Jäger G, Wulfhorst H, Zeithammel EU et al (2011) Screening of cellulases for biofuel production: online monitoring of the enzymatic hydrolysis of insoluble cellulose using high-throughput scattered light detection. Biotechnol J 6:74–85. doi:10.1002/biot.201000387
94. Oliveira AF, Pessoa ACSN, Bastos RG, de la Torre LG (2016) Microfluidic tools toward industrial biotechnology. Biotechnol Prog. doi:10.1002/btpr.2350
95. Blesken C, Olfers T, Grimm A, Frische N (2016) The microfluidic bioreactor for a new era of bioprocess development. Eng Life Sci 16:190–193. doi:10.1002/elsc.201500026
96. Hegab HM, ElMekawy A, Stakenborg T (2013) Review of microfluidic microbioreactor technology for high-throughput submerged microbiological cultivation. Biomicrofluidics. doi:10.1063/1.4799966
97. Puskeiler R, Kusterer A, John GT, Weuster-Botz D (2005) Miniature bioreactors for automated high-throughput bioprocess design (HTBD): reproducibility of parallel fed-batch cultivations with Escherichia coli. Biotechnol Appl Biochem 42:227–235. doi:10.1042/BA20040197
98. Funke M, Buchenauer A, Schnakenberg U et al (2010) Microfluidic biolector-microfluidic bioprocess control in microtiter plates. Biotechnol Bioeng 107:497–505. doi:10.1002/bit.22825
99. Gebhardt G, Hortsch R, Kaufmann K et al (2011) A new microfluidic concept for parallel operated milliliter-scale stirred tank bioreactors. Biotechnol Prog 27:684–690. doi:10.1002/btpr.570
100. Bras EJS, Chu V, Aires-Barros MR et al (2016) A microfluidic platform for physical entrapment of yeast cells with continuous production of invertase. J Chem Technol Biotechnol. doi:10.1002/jctb.5010
101. Schäpper D, Alam MNHZ, Szita N et al (2009) Application of microbioreactors in fermentation process development: a review. Anal Bioanal Chem 395:679–695. doi:10.1007/s00216-009-2955-x
102. de Jong J, Lammertink RGH, Wessling M (2006) Membranes and microfluidics: a review. Lab Chip 6:1125–1139. doi:10.1039/b603275c
103. Coutte F, Lecouturier D, Leclère V et al (2013) New integrated bioprocess for the continuous production, extraction and purification of lipopeptides produced by Bacillus subtilis in membrane bioreactor. Process Biochem 48:25–32. doi:10.1016/j.procbio.2012.10.005
104. Zanzotto A, Szita N, Boccazzi P et al (2004) Membrane-aerated microbioreactor for high-throughput bioprocessing. Biotechnol Bioeng 87:243–254. doi:10.1002/bit.20140
105. Daubert I, Mercier-Bonin M, Maranges C et al (2003) Why and how membrane bioreactors with unsteady filtration conditions can improve the efficiency of biological processes. Ann N Y Acad Sci 984:420–435
106. Alam MNHZ, Pinelo M, Samanta K et al (2011) A continuous membrane microbioreactor system for development of integrated pectin modification and separation processes. Chem Eng J 167:418–426. doi:10.1016/j.cej.2010.09.082
107. Coutte F, Lecouturier D, Firdaous L et al (2016) Recent trends in membrane bioreactors. Current developments in biotechnology and bioengineering. Recent Trends Membr Bioreact (In press)
108. Zavrel M, Bross D, Funke M et al (2009) High-throughput screening for ionic liquids dissolving (ligno-)cellulose. Bioresour Technol 100:2580–2587. doi:10.1016/j.biortech.2008.11.052
109. Kirk TV, Szita N (2013) Oxygen transfer characteristics of miniaturized bioreactor systems. Biotechnol Bioeng 110:1005–1019. doi:10.1002/bit.24824
110. Betts JI, Baganz F (2006) Miniature bioreactors: current practices and future opportunities. Microb Cell Fact 5:21. doi:10.1186/1475-2859-5-21
111. Kim BJ, Diao J, Shuler ML (2012) Mini-scale bioprocessing systems for highly parallel animal cell cultures. Biotechnol Prog 28:595–607. doi:10.1002/btpr.1554
112. Frachon E, Bondet V, Munier-Lehmann H, Bellalou J (2006) Multiple microfermentor battery: a versatile tool for use with automated parallel cultures of microorganisms producing recombinant proteins and for optimization of cultivation protocols. Appl Environ Microbiol 72:5225–5231. doi:10.1128/AEM.00239-06
113. Motta Dos Santos LF, Coutte F, Ravallec R et al (2016) An improvement of surfactin production by B. subtilis BBG131 using design of experiments in microbioreactors and continuous process in bubbleless membrane bioreactor. Bioresour Technol. doi:10.1016/j.biortech.2016.07.053
114. Riedlberger P, Weuster-Botz D (2012) New miniature stirred-tank bioreactors for parallel study of enzymatic biomass hydrolysis. Bioresour Technol 106:138–146. doi:10.1016/j.biortech.2011.12.019
115. Nunes MAP, Fernandes PCB, Ribeiro MHL (2013) Microtiter plates versus stirred mini-bioreactors in biocatalysis: a scalable approach. Bioresour Technol 136:30–40. doi:10.1016/j.biortech.2013.02.057
116. Delvigne F, Brognaux A, Francis F et al (2011) Green fluorescent protein (GFP) leakage from microbial biosensors provides useful information for the evaluation of the scale-down effect. Biotechnol J 6:968–978. doi:10.1002/biot.201000410
117. Brognaux A, Thonart P, Delvigne F et al (2013) Direct and indirect use of GFP whole cell biosensors for the assessment of bioprocess performances: design of milliliter scale-down bioreactors. Biotechnol Prog 29:48–59. doi:10.1002/btpr.1660
118. Guiochon G, Beaver LA (2011) Separation science is the key to successful biopharmaceuticals. J Chromatogr A 1218:8836–8858. doi:10.1016/j.chroma.2011.09.008
119. Shukla AA, Hubbard B, Tressel T et al (2007) Downstream processing of monoclonal antibodies—application of platform approaches. J Chromatogr B Anal Technol Biomed Life Sci 848:28–39. doi:10.1016/j.jchromb.2006.09.026
120. Kuhad RC, Deswal D, Sharma S et al (2016) Revisiting cellulase production and redefining current strategies based on major challenges. Renew Sustain Energy Rev 55:249–272. doi:10.1016/j.rser.2015.10.132
121. Nfor BK, Verhaert PDEM, van der Wielen LAM et al (2009) Rational and systematic protein purification process development: the next generation. Trends Biotechnol 27:673–679. doi:10.1016/j.tibtech.2009.09.002
122. Łacki KM, Lacki KM (2014) High throughput process development in biomanufacturing. Curr Opin Chem Eng 6:25–32. doi:10.1016/j.coche.2014.08.004
123. Hanke AT, Ottens M (2014) Purifying biopharmaceuticals: knowledge-based chromatographic process development. Trends Biotechnol 32:210–220. doi:10.1016/j.tibtech.2014.02.001
124. Jungbauer A (2013) Continuous downstream processing of biopharmaceuticals. Trends Biotechnol 31:479–492. doi:10.1016/j.tibtech.2013.05.011
125. Carapito R, Gallet B, Zapun A, Vernet T (2006) Automated high-throughput process for site-directed mutagenesis, production, purification, and kinetic characterization of enzymes. Anal Biochem 355:110–116. doi:10.1016/j.ab.2006.04.047
126. Yoo D, Provchy J, Park C et al (2014) Automated high-throughput protein purification using an ÄKTApurifier and a CETAC autosampler. J Chromatogr A 1344:23–30. doi:10.1016/j.chroma.2014.04.014
127. Merrill AH, Sullards MC, Allegood JC et al (2005) Sphingolipidomics: high-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry. Methods 36:207–224. doi:10.1016/j.ymeth.2005.01.009
128. de Boer AR, Letzel T, van Elswijk DA et al (2004) On-line coupling of high-performance liquid chromatography to a continuous-flow enzyme assay based on electrospray ionization mass spectrometry. Anal Chem 76:3155–3161. doi:10.1021/ac035380w
129. Gillet LC, Leitner A, Aebersold R (2015) Mass spectrometry applied to bottom-up proteomics: entering the high-throughput era for hypothesis testing
130. Swaney DL, Villén J (2016) Proteomic analysis of protein posttranslational modifications by mass spectrometry. Cold Spring Harbor Protoc 2016:pdb.top077743. doi:10.1101/pdb.top077743
131. McCullough B, Gaskell S (2009) Using electrospray ionisation mass spectrometry to study non-covalent interactions. Comb Chem High Throughput Screen 12:203–211. doi:10.2174/138620709787315463
132. Gingras A-C, Gstaiger M, Raught B, Aebersold R (2007) Analysis of protein complexes using mass spectrometry. Nat Rev Mol Cell Biol 8:645–654. doi:10.1038/nrm2208
133. Smits AH, Vermeulen M (2016) Characterizing protein–protein interactions using mass spectrometry: challenges and opportunities. Trends Biotechnol. doi:10.1016/j.tibtech.2016.02.014
134. Van Veen SQ, Claas ECJ, Kuijper EJ (2010) High-throughput identification of bacteria and yeast by matrix-assisted laser desorption ionization-time of flight mass spectrometry in conventional medical microbiology laboratories. J Clin Microbiol 48:900–907. doi:10.1128/JCM.02071-09
135. Sandrin TR, Goldstein JE, Schumaker S (2013) MALDI TOF MS profiling of bacteria at the strain level: a review. Mass Spectrom Rev. doi:10.1002/mas
136. Cornett DS, Reyzer ML, Chaurand P, Caprioli RM (2007) MALDI imaging mass spectrometry: molecular snapshots of biochemical systems. Nat Methods 4:828–833. doi:10.1038/nmeth1094
137. Bodzon-Kulakowska A, Bierczynska-Krzysik A, Dylag T et al (2006) Methods for samples preparation in proteomic research. J Chromatogr B Analyt Technol Biomed Life Sci 849:1–31
138. Barkal LJ, Theberge AB, Guo C et al (2016) Microbial metabolomics in open microscale platforms. Nat Commun 7:1–11. doi:10.1038/ncomms10610
139. de Raad M, Fischer CR, Northen TR (2015) High-throughput platforms for metabolomics. Curr Opin Chem Biol 30:7–13. doi:10.1016/j.cbpa.2015.10.012
140. Welker M (2011) Proteomics for routine identification of microorganisms. Proteomics 11:3143–3153. doi:10.1002/pmic.201100049
141. Schey KL, Hachey AJ, Rose KM, Grey AC (2016) MALDI imaging mass spectrometry of Pacific White Shrimp L. vannamei and identification of abdominal muscle. Proteins. doi:10.1002/pmic.201500531
142. De Rond T, Peralta-Yahya P, Cheng X et al (2013) Versatile synthesis of probes for high-throughput enzyme activity screening. Anal Bioanal Chem 405:4969–4973. doi:10.1007/s00216-013-6888-z
143. Chen B, Peng Y, Valeja SG et al (2016) Online hydrophobic interaction chromatography–mass spectrometry for top-down proteomics. Anal Chem. doi:10.1021/acs.analchem.5b04285
144. Catherman AD, Skinner OS, Kelleher NL (2014) Top down proteomics: facts and perspectives. Biochem Biophys Res Commun 445:683–693. doi:10.1016/j.bbrc.2014.02.041
145. Mayne J, Ning Z, Zhang X et al (2016) Bottom-up proteomics (2013–2015): keeping up in the era of systems biology. Anal Chem 88:95–121. doi:10.1021/acs.analchem.5b04230
146. Qi Y, Volmer DA (2016) Structural analysis of small to medium-sized molecules by mass spectrometry after electron-ion fragmentation (ExD) reactions. Analyst 141:794–806. doi:10.1039/c5an02171e
147. Hu A, Noble WS, Wolf-Yadlin A (2016) Technical advances in proteomics: new developments in data-independent acquisition. F1000Research. doi:10.12688/f1000research.7042.1
148. Chen P (2003) Electrospray ionization tandem mass spectrometry in high-throughput screening of homogeneous catalysts. Angew Chem Int Ed 42:2832–2847. doi:10.1002/anie.200200560
149. Ng ESM, Yang F, Kameyama A et al (2005) High-throughput screening for enzyme inhibitors using frontal affinity chromatography with liquid chromatography and mass spectrometry. Anal Chem 77:6125–6133. doi:10.1021/ac051131r
150. Yi X, Hao Y, Xia N et al (2013) Sensitive and continuous screening of inhibitors of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) at single SPR chips. Anal Chem 85:3660–3666. doi:10.1021/ac303624z
151. Ahmad S, Hughes MA, Johnson GL, Scott JE (2013) Development and validation of a high-throughput intrinsic ATPase activity assay for the discovery of MEKK2 inhibitors. J Biomol Screen 18:388–399. doi:10.1177/1087057112466430
152. Greis KD (2006) Mass spectrometry for enzyme assays and inhibitor screening: an emerging application in pharmaceutical research. Mass Spectrom Rev 26:324–339. doi:10.1002/mas.20127
153. Domínguez JM, Fuertes A, Orozco L et al (2012) Evidence for irreversible inhibition of glycogen synthase kinase-3β by tideglusib. J Biol Chem 287:893–904. doi:10.1074/jbc.M111.306472
154. Song XS, Zhang J, Chen X et al (2015) Identification of DGAT2 inhibitors using mass spectrometry. J Biomol Screen. doi:10.1177/1087057115607463
155. Reetz MT, Becker MH (1999) Enantioselective catalysts. Communications 1758–1761
156. Schrader W, Eipper A, Pugh DJ, Reetz MT (2002) Second-generation MS-based high-throughput screening system for enantioselective catalysts and biocatalysts. Can J Chem 80:626–632. doi:10.1139/v02-069
157. Bakhtiar R, Ramos L, Tse FL (2001) Use of atmospheric pressure ionization mass spectrometry in enantioselective liquid chromatography. Chirality 13:63–74. doi:10.1002/1520-636X(2001)13:2<63:AID-CHIR1000>3.0.CO;2-5
158. Schug K (2007) Solution phase enantioselective recognition and discrimination by electrospray ionization–mass spectrometry: state-of-the-art, methods, and an eye towards increased throughput measurements. Comb Chem High Throughput Screen 10:301–316. doi:10.2174/138620707781662790
159. Kanie O, Shioiri Y, Ogata K et al (2016) Diastereomeric resolution directed towards chirality determination focussing on gas-phase energetics of coordinated sodium dissociation. Sci Rep 6:24005. doi:10.1038/srep24005
160. Lepère V, Le Barbu-Debus K, Clavaguéra C et al (2015) Chirality-dependent structuration of protonated or sodiated polyphenylalanines: IRMPD and ion mobility studies. Phys Chem Chem Phys. doi:10.1039/C5CP06768E.10.1039/C5CP06768E
161. Dancík V, Addona TA, Clauser KR et al (2004) De novo peptide sequencing via tandem mass spectrometry. J Comput Biol J Comput Mol Cell Biol 6:327–342. doi:10.1089/106652799318300
162. Trimpin S (2016) “Magic” ionization mass spectrometry. J Am Soc Mass Spectrom 27:4–21. doi:10.1007/s13361-015-1253-4
163. Cramer R (2015) Advances in MALDI and laser-induced soft ionization mass spectrometry. Adv MALDI Laser Induc Soft Ioniz Mass Spectrom. doi:10.1007/978-3-319-04819-2
164. Smoluch M, Mielczarek P, Silberring J (2016) Plasma-based ambient ionization mass spectrometry in bioanalytical sciences. Mass Spectrom Rev 35:22–34. doi:10.1002/mas.21460
165. Gordon LJ, Allen M, Artursson P et al (2016) Direct measurement of intracellular compound concentration by rapidfire mass spectrometry offers insights into cell permeability. J Biomol Screen 21:156–164. doi:10.1177/1087057115604141
166. Chumbley CW, Reyzer ML, Allen JL et al (2016) Absolute quantitative MALDI imaging mass spectrometry: a case of rifampicin in liver tissues. Anal Chem 88:2392–2398. doi:10.1021/acs.analchem.5b04409
167. Holding AN (2015) XL-MS: protein cross-linking coupled with mass spectrometry. Methods 89:54–63. doi:10.1016/j.ymeth.2015.06.010
168. Leitner A, Faini M, Stengel F, Aebersold R (2016) Crosslinking and mass spectrometry: an integrated technology to understand the structure and function of molecular machines. Trends Biochem Sci 41:20–32. doi:10.1016/j.tibs.2015.10.008
169. Ghaste M, Mistrik R, Shulaev V (2016) Applications of Fourier transform ion cyclotron resonance (FT-ICR) and orbitrap based high resolution mass spectrometry in metabolomics and lipidomics. Int J Mol Sci 17:816. doi:10.3390/ijms17060816
170. Ma X, Ouyang Z (2016) Ambient ionization and miniature mass spectrometry system for chemical and biological analysis. TrAC Trends Anal Chem. doi:10.1016/j.trac.2016.04.009
171. Cetina DM, Giraldo GI, Orrego CE (2011) Application of response surface design to solvent, temperature and lipase selection for optimal monoglyceride production. J Mol Catal B Enzym 72:13–19. doi:10.1016/j.molcatb.2011.04.017
172. Corrêa FDA, Sutili FK, Miranda LSM et al (2012) Epoxidation of oleic acid catalyzed by PSCI-amano lipase optimized by experimental design. J Mol Catal B Enzym 81:7–11. doi:10.1016/j.molcatb.2012.03.011
173. Gonçalves KM, Sutili FK, Leite SGF et al (2012) Palm oil hydrolysis catalyzed by lipases under ultrasound irradiation—the use of experimental design as a tool for variables evaluation. Ultrason Sonochem 19:232–236. doi:10.1016/j.ultsonch.2011.06.017
174. Lee A, Chaibakhsh N, Rahman MBA et al (2010) Optimized enzymatic synthesis of levulinate ester in solvent-free system. Ind Crops Prod 32:246–251. doi:10.1016/j.indcrop.2010.04.022
175. Heuson E, Petit J-L, Debard A et al (2016) Continuous colorimetric screening assays for the detection of specific l- or d-α-amino acid transaminases in enzyme libraries. Appl Microbiol Biotechnol 100:397–408. doi:10.1007/s00253-015-6988-0
176. Lerin LA, Richetti A, Dallago R et al (2012) Enzymatic synthesis of ascorbyl palmitate in organic solvents: process optimization and kinetic evaluation. Food Bioprocess Technol 5:1068–1076. doi:10.1007/s11947-010-0398-1
177. Abildskov J, Van Leeuwen MB, Boeriu CG, Van Den Broek LAM (2013) Computer-aided solvent screening for biocatalysis. J Mol Catal B Enzym 85–86:200–213. doi:10.1016/j.molcatb.2012.09.012
178. Rosa SM, Soria MA, Vlez CG, Galvagno MA (2010) Improvement of a two-stage fermentation process for docosahexaenoic acid production by Aurantiochytrium limacinum SR21 applying statistical experimental designs and data analysis. Bioresour Technol 101:2367–2374. doi:10.1016/j.biortech.2009.11.056
179. Godoy MG, Gutarra MLE, Castro AM et al (2011) Adding value to a toxic residue from the biodiesel industry: production of two distinct pool of lipases from Penicillium simplicissimum in castor bean waste. J Ind Microbiol Biotechnol 38:945–953. doi:10.1007/s10295-010-0865-8
180. Malik M, Ganguli A, Ghosh M (2012) Modeling of permeabilization process in Pseudomonas putida G7 for enhanced limonin bioconversion. Appl Microbiol Biotechnol 95:223–231. doi:10.1007/s00253-012-3880-z
181. Lattanzio VMT, Von Holst C, Visconti A (2013) Experimental design for in-house validation of a screening immunoassay kit. The case of a multiplex dipstick for Fusarium mycotoxins in cereals. Anal Bioanal Chem 405:7773–7782. doi:10.1007/s00216-013-6922-1
182. Rios-Solis L, Bayir N, Halim M et al (2013) Non-linear kinetic modelling of reversible bioconversions: application to the transaminase catalyzed synthesis of chiral amino-alcohols. Biochem Eng J 73:38–48. doi:10.1016/j.bej.2013.01.010
183. Fu Q, Zhang C, Lin Z et al (2016) Rapid screening and identification of compounds with DNA-binding activity from folium citri reticulatae using on-line HPLC-DAD-MS(n) coupled with a post column fluorescence detection system. Food Chem 192:250–259. doi:10.1016/j.foodchem.2015.07.009
184. Müller MM, Hausmann R (2011) Regulatory and metabolic network of rhamnolipid biosynthesis: traditional and advanced engineering towards biotechnological production. Appl Microbiol Biotechnol 91:251–264. doi:10.1007/s00253-011-3368-2
185. Brooks KM, Hampel KJ (2011) Rapid steps in the glmS ribozyme catalytic pathway: cation and ligand requirements. Biochemistry 50:2424–2433. doi:10.1021/bi101842u
186. Bøjstrup M, Marri L, Lok F, Hindsgaul O (2015) A chromogenic assay suitable for high-throughput determination of limit dextrinase activity in barley malt extracts. J Agric Food Chem 63:10873–10878. doi:10.1021/acs.jafc.5b04596