Role of Biocatalysis in Sustainable Chemistry.

Based on the principles and metrics of green chemistry and sustainable development, biocatalysis is both a green and sustainable technology. This is largely a result of the spectacular advances in molecular biology and biotechnology achieved in the past two decades. Protein engineering has enabled the optimization of existing enzymes and the invention of entirely new biocatalytic reactions that were previously unknown in Nature. It is now eminently feasible to develop enzymatic transformations to fit predefined parameters, resulting in processes that are truly sustainable by design. This approach has successfully been applied, for example, in the industrial synthesis of active pharmaceutical ingredients. In addition to the use of protein engineering, other aspects of biocatalysis engineering, such as substrate, medium, and reactor engineering, can be utilized to improve the efficiency and cost-effectiveness and, hence, the sustainability of biocatalytic reactions. Furthermore, immobilization of an enzyme can improve its stability and enable its reuse multiple times, resulting in better performance and commercial viability. Consequently, biocatalysis is being widely applied in the production of pharmaceuticals and some commodity chemicals. Moreover, its broader application will be further stimulated in the future by the emerging biobased economy.

[1]  S. Talekar,et al.  Parameters in preparation and characterization of cross linked enzyme aggregates (CLEAs) , 2013 .

[2]  Frank Hollmann,et al.  On the (Un)greenness of Biocatalysis: Some Challenging Figures and Some Promising Options , 2015, Front. Microbiol..

[3]  G. Baker,et al.  Protease activation in glycerol-based deep eutectic solvents. , 2011, Journal of molecular catalysis. B, Enzymatic.

[4]  G. Matcham,et al.  Biocatalysis for chiral intermediates : Meeting commercial and technical challenges , 1996 .

[5]  Roger A. Sheldon,et al.  Effective resolution of 1-phenyl ethanol by Candida antarctica lipase B catalysed acylation with vinyl acetate in protic ionic liquids (PILs) , 2012 .

[6]  H. Cabana,et al.  Magnetic cross-linked laccase aggregates--bioremediation tool for decolorization of distinct classes of recalcitrant dyes. , 2014, The Science of the total environment.

[7]  Andreas S Bommarius,et al.  Stabilizing biocatalysts. , 2013, Chemical Society reviews.

[8]  Wei Zhang,et al.  Studies of Fe3O4-chitosan nanoparticles prepared by co-precipitation under the magnetic field for lipase immobilization , 2011 .

[9]  M. Kļaviņš,et al.  (2-Hydroxyethyl)ammonium Lactates—Highly Biodegradable and Essentially Non-Toxic Ionic Liquids , 2011 .

[10]  Ramesh N. Patel Green Biocatalysis: Patel/Green Biocatalysis , 2016 .

[11]  Richard J Ingham,et al.  Organic synthesis: march of the machines. , 2015, Angewandte Chemie.

[12]  Flavien Susanne,et al.  Continuous flow synthesis. A pharma perspective. , 2012, Journal of medicinal chemistry.

[13]  Alexei Lapkin,et al.  Green chemistry metrics: measuring and monitoring sustainable processes , 2008 .

[14]  P. Villeneuve,et al.  Deep eutectic solvents: Synthesis, application, and focus on lipase‐catalyzed reactions , 2013 .

[15]  John M. Woodley,et al.  Engineering of Biocatalysts and Biocatalytic Processes , 2014, Topics in Catalysis.

[16]  Pengfei Zhou,et al.  Chemoenzymatic epoxidation of alkenes with Candida antarctica lipase B and hydrogen peroxide in deep eutectic solvents , 2017 .

[17]  Gjalt W Huisman,et al.  On the development of new biocatalytic processes for practical pharmaceutical synthesis. , 2013, Current opinion in chemical biology.

[18]  R. Varma,et al.  Nano-magnetite (Fe3O4) as a support for recyclable catalysts in the development of sustainable methodologies. , 2013, Chemical Society reviews.

[19]  R. Sheldon Cross-Linked Enzyme Aggregates as Industrial Biocatalysts , 2011 .

[20]  John C Whitman,et al.  Improving catalytic function by ProSAR-driven enzyme evolution , 2007, Nature Biotechnology.

[21]  Rafiqul Gani,et al.  Solvent selection methodology for pharmaceutical processes: Solvent swap , 2016 .

[22]  Wolf-Dieter Fessner,et al.  Systems Biocatalysis: Development and engineering of cell-free "artificial metabolisms" for preparative multi-enzymatic synthesis. , 2015, New biotechnology.

[23]  S. Çelebi,et al.  Performance of immobilized glucoamylase in a magnetically stabilized fluidized bed reactor (MSFBR) , 2000 .

[24]  J. Woodley,et al.  Boron based separations for in situ recovery of L-erythrulose from transketolase-catalyzed condensation. , 1997, Biotechnology and bioengineering.

[25]  Matthew D Truppo,et al.  Biocatalysis in the Pharmaceutical Industry: The Need for Speed. , 2017, ACS medicinal chemistry letters.

[26]  H. Toma,et al.  Superparamagnetic nanoparticles as versatile carriers and supporting materials for enzymes , 2013 .

[27]  Spiros N Agathos,et al.  Utilization of cross‐linked laccase aggregates in a perfusion basket reactor for the continuous elimination of endocrine‐disrupting chemicals , 2009, Biotechnology and bioengineering.

[28]  Frances H. Arnold,et al.  Enantioselective Enzyme-Catalyzed Aziridination Enabled by Active-Site Evolution of a Cytochrome P450 , 2015, ACS central science.

[29]  G. Huisman,et al.  Engineering the third wave of biocatalysis , 2012, Nature.

[30]  Volker Hessel,et al.  Lipase-Based Biocatalytic Flow Process in a Packed-Bed Microreactor , 2013 .

[31]  Emil Byström,et al.  Efficient Biocatalysis with Immobilized Enzymes or Encapsulated Whole Cell Microorganism by Using the SpinChem Reactor System , 2013 .

[32]  W. Leuchtenberger,et al.  Biotechnological production of amino acids and derivatives: current status and prospects , 2005, Applied Microbiology and Biotechnology.

[33]  Jian Dong Cui,et al.  Optimization protocols and improved strategies of cross-linked enzyme aggregates technology: current development and future challenges , 2015, Critical reviews in biotechnology.

[34]  J. Wegner,et al.  Flow Chemistry – A Key Enabling Technology for (Multistep) Organic Synthesis , 2012 .

[35]  H. Gunaratne,et al.  Novel biocompatible cholinium-based ionic liquids—toxicity and biodegradability , 2010 .

[36]  Concepción Jiménez-González,et al.  Fast life cycle assessment of synthetic chemistry (FLASC™) tool , 2007 .

[37]  Neal G. Anderson,et al.  Using Continuous Processes to Increase Production , 2012 .

[38]  Vesna Mitchell,et al.  Development of a Biocatalytic Process as an Alternative to the (−)-DIP-Cl-Mediated Asymmetric Reduction of a Key Intermediate of Montelukast , 2010 .

[39]  John Andraos,et al.  Choosing the Greenest Synthesis: A Multivariate Metric Green Chemistry Exercise , 2012 .

[40]  Martina Letizia Contente,et al.  Continuous flow biocatalysis: production and in-line purification of amines by immobilised transaminase from Halomonas elongata , 2017 .

[41]  F. V. D. Velde,et al.  Enantioselective sulfoxidation mediated by vanadium-incorporated phytase: a hydrolase acting as a peroxidase , 1998 .

[42]  D. Clark,et al.  Salts dramatically enhance activity of enzymes suspended in organic solvents , 1994 .

[43]  Romas J. Kazlauskas,et al.  Biocatalysis for green chemistry and chemical process development , 2011 .

[44]  P. Villeneuve,et al.  Evaluation of deep eutectic solvent-water binary mixtures for lipase-catalyzed lipophilization of phenolic acids , 2013 .

[45]  Muhammad Moniruzzaman,et al.  Recent advances of enzymatic reactions in ionic liquids , 2010 .

[46]  Frances H. Arnold,et al.  Directed evolution of a para-nitrobenzyl esterase for aqueous-organic solvents , 1996, Nature Biotechnology.

[47]  M. J. Cocero,et al.  Influence of the enzyme concentration on the phase behaviour for developing a homogeneous enzymatic reaction in ionic liquid–CO2 media , 2008 .

[48]  J. Woodley,et al.  Guidelines and Cost Analysis for Catalyst Production in Biocatalytic Processes , 2011 .

[49]  U. Bornscheuer,et al.  Cascade catalysis--strategies and challenges en route to preparative synthetic biology. , 2015, Chemical communications.

[50]  Andrew Currin,et al.  Synthetic biology for the directed evolution of protein biocatalysts: navigating sequence space intelligently , 2014, Chemical Society reviews.

[51]  K. Edler,et al.  Liquid structure of the choline chloride-urea deep eutectic solvent (reline) from neutron diffraction and atomistic modelling , 2016 .

[52]  R. Sheldon,et al.  Preparation, optimization, and structures of cross‐linked enzyme aggregates (CLEAs) , 2004, Biotechnology and bioengineering.

[53]  S. Ha,et al.  One-pot bioconversion of sucrose to trehalose using enzymatic sequential reactions in combined cross-linked enzyme aggregates. , 2013, Bioresource technology.

[54]  M. Hartmann,et al.  Recent Progress in Biocatalysis with Enzymes Immobilized on Mesoporous Hosts , 2012, Topics in Catalysis.

[55]  S. Jia,et al.  Hybrid Cross-Linked Lipase Aggregates with Magnetic Nanoparticles: A Robust and Recyclable Biocatalysis for the Epoxidation of Oleic Acid. , 2016, Journal of agricultural and food chemistry.

[56]  Raymond L. Smith,et al.  Using GREENSCOPE indicators for sustainable computer-aided process evaluation and design , 2015, Comput. Chem. Eng..

[57]  Polona Žnidaršič-Plazl,et al.  Modelling and experimental studies on lipase-catalyzed isoamyl acetate synthesis in a microreactor , 2009 .

[58]  Joerg H. Schrittwieser,et al.  One-pot combination of enzyme and Pd nanoparticle catalysis for the synthesis of enantiomerically pure 1,2-amino alcohols , 2013 .

[59]  R. Kazlauskas,et al.  Manganese-substituted carbonic anhydrase as a new peroxidase. , 2006, Chemistry.

[60]  Nigel S Scrutton,et al.  Systematic methodology for the development of biocatalytic hydrogen-borrowing cascades: application to the synthesis of chiral α-substituted carboxylic acids from α-substituted α,β-unsaturated aldehydes. , 2015, Organic & biomolecular chemistry.

[61]  Friedrich Srienc,et al.  Hydrolase-catalyzed biotransformations in deep eutectic solvents. , 2008, Chemical communications.

[62]  Neil R Thomas,et al.  Biocatalysis in supercritical fluids, in fluorous solvents, and under solvent-free conditions. , 2007, Chemical reviews.

[63]  Klaus Buchholz,et al.  A breakthrough in enzyme technology to fight penicillin resistance—industrial application of penicillin amidase , 2016, Applied Microbiology and Biotechnology.

[64]  Bruce Blumberg,et al.  Endocrine disrupting chemicals , 2011, The Journal of Steroid Biochemistry and Molecular Biology.

[65]  Daniel N. Tran,et al.  Perspective of Recent Progress in Immobilization of Enzymes , 2011 .

[66]  John M Woodley,et al.  Process technology for multi-enzymatic reaction systems. , 2012, Bioresource technology.

[67]  Jung-Min Choi,et al.  Industrial applications of enzyme biocatalysis: Current status and future aspects. , 2015, Biotechnology advances.

[68]  D. Wei,et al.  Optimisation of enzymatic synthesis of cefaclor with in situ product removal and continuous acyl donor feeding , 2007 .

[69]  Martin Hartmann,et al.  Immobilization of enzymes on porous silicas--benefits and challenges. , 2013, Chemical Society reviews.

[70]  R. Sheldon Characteristic features and biotechnological applications of cross-linked enzyme aggregates (CLEAs) , 2011, Applied Microbiology and Biotechnology.

[71]  Emma L. Smith,et al.  Deep eutectic solvents (DESs) and their applications. , 2014, Chemical reviews.

[72]  Manfred T Reetz,et al.  What are the Limitations of Enzymes in Synthetic Organic Chemistry? , 2016, Chemical record.

[73]  B. Bachmann,et al.  Five‐Component Cascade Synthesis of Nucleotide Analogues in an Engineered Self‐Immobilized Enzyme Aggregate , 2009, Chembiochem : a European journal of chemical biology.

[74]  Ramesh N. Patel Biocatalysis in the pharmaceutical and biotechnology industries , 2006 .

[75]  C. Carlesi,et al.  Deep Eutectic Solvents for Organocatalysis, Biotransformations, and Multistep Organocatalyst/Enzyme Combinations , 2016 .

[76]  Jim Lalonde,et al.  Highly engineered biocatalysts for efficient small molecule pharmaceutical synthesis. , 2016, Current opinion in biotechnology.

[77]  Brahim Benyahia,et al.  Development of a Multi-Step Synthesis and Workup Sequence for an Integrated, Continuous Manufacturing Process of a Pharmaceutical , 2014 .

[78]  Johan Alftrén,et al.  Immobilization of cellulase mixtures on magnetic particles for hydrolysis of lignocellulose and ease of recycling , 2014 .

[79]  Ian R. Baxendale,et al.  The integration of flow reactors into synthetic organic chemistry , 2013 .

[80]  G. Lidén,et al.  A short review on SSF – an interesting process option for ethanol production from lignocellulosic feedstocks , 2008, Biotechnology for biofuels.

[81]  Shamraja S. Nadar,et al.  Novel magnetic cross-linked enzyme aggregates (magnetic CLEAs) of alpha amylase. , 2012, Bioresource technology.

[82]  J. Littlechild,et al.  Immobilization of thermophilic enzymes in miniaturized flow reactors. , 2007, Biochemical Society transactions.

[83]  Shiro Saka,et al.  Various pretreatments of lignocellulosics. , 2016, Bioresource technology.

[84]  Roger A. Sheldon,et al.  Enantioselective acylation of chiral amines catalysed by serine hydrolases , 2004 .

[85]  E. Jong,et al.  Product developments in the bio‐based chemicals arena , 2012 .

[86]  U. Hanefeld,et al.  Understanding Enzyme Immobilization , 2009 .

[87]  Andreas Schmid,et al.  Biocatalytic Production of Catechols Using a High Pressure Tube-in-Tube Segmented Flow Microreactor , 2014 .

[88]  Rolf Dach,et al.  The Eight Criteria Defining a Good Chemical Manufacturing Process , 2012 .

[89]  Lucia Gardossi,et al.  Understanding enzyme immobilisation. , 2009, Chemical Society reviews.

[90]  Gregory Stephanopoulos,et al.  Synthetic biology and metabolic engineering. , 2012, ACS synthetic biology.

[91]  M. de la Fuente Revenga,et al.  Deep eutectic solvents (DESs) are viable cosolvents for enzyme-catalyzed epoxide hydrolysis. , 2010, Journal of biotechnology.

[92]  B. Tang,et al.  Immobilized cellulase on Fe3O4 nanoparticles as a magnetically recoverable biocatalyst for the decomposition of corncob , 2016 .

[93]  R. Bogel-Lukasik Ionic Liquids in the Biorefinery Concept: Challenges and Perspectives , 2015 .

[94]  Lin Li,et al.  Preparation and Properties of Cross-Linked Enzyme Aggregates of Cellulase , 2012 .

[95]  H. Kawaguchi,et al.  Bioprocessing of bio-based chemicals produced from lignocellulosic feedstocks. , 2016, Current opinion in biotechnology.

[96]  Johan Alftrén,et al.  Covalent Immobilization of β-Glucosidase on Magnetic Particles for Lignocellulose Hydrolysis , 2013, Applied Biochemistry and Biotechnology.

[97]  Jack Liang,et al.  Practical chiral alcohol manufacture using ketoreductases. , 2010, Current opinion in chemical biology.

[98]  Frank Hollmann,et al.  How Green is Biocatalysis? To Calculate is To Know , 2014 .

[99]  R. Sheldon CHAPTER 2:Biocatalysis in Ionic Liquids , 2014 .

[100]  Riccardo Porta,et al.  Flow Chemistry: Recent Developments in the Synthesis of Pharmaceutical Products , 2016 .

[101]  Concepción Jiménez-González,et al.  Expanding the Boundaries: Developing a Streamlined Tool for Eco-Footprinting of Pharmaceuticals , 2013 .

[102]  R. Illias,et al.  Silanized maghemite for cross-linked enzyme aggregates of recombinant xylanase from Trichoderma reesei , 2016 .

[103]  Michiel Janssen,et al.  Room-temperature ionic liquids that dissolve carbohydrates in high concentrations , 2005 .

[104]  Kazunori Watanabe,et al.  Control of enantioselectivity of lipase-catalyzed esterification in supercritical carbon dioxide by tuning the pressure and temperature , 2003 .

[105]  Pablo Domínguez de María,et al.  Benzaldehyde lyase (BAL)-catalyzed enantioselective CC bond formation in deep-eutectic-solvents–buffer mixtures , 2014 .

[106]  Sven Reimann,et al.  Phosphine-modified Pd/Al2O3 for asymmetric allylic substitution , 2008 .

[107]  J. V. D. Waal,et al.  Catalytic Process Development for Renewable Materials: IMHOF:CAT PROCESS DEVE O-BK , 2013 .

[108]  Linqiu Cao,et al.  Carrier-bound Immobilized Enzymes: Principles, Application and Design , 2005 .

[109]  Pablo Domínguez de María,et al.  Chymotrypsin‐Catalyzed Peptide Synthesis in Deep Eutectic Solvents , 2013 .

[110]  J. Woodley,et al.  Application of environmental and economic metrics to guide the development of biocatalytic processes , 2014 .

[111]  John M Woodley,et al.  The search for the ideal biocatalyst , 2002, Nature Biotechnology.

[112]  Gary J. Lye,et al.  Microfluidic multi-input reactor for biocatalytic synthesis using transketolase☆ , 2013, Journal of molecular catalysis. B, Enzymatic.

[113]  Virendra K Rathod,et al.  A magnetic tri-enzyme nanobiocatalyst for fruit juice clarification. , 2016, Food chemistry.

[114]  Zhoutong Sun,et al.  New Concepts for Increasing the Efficiency in Directed Evolution of Stereoselective Enzymes. , 2016, Chemistry.

[115]  R. Sheldon,et al.  Enzymatic ammoniolysis of amino acid derivatives , 2010 .

[116]  Ann Anton,et al.  Green biodiesel production: a review on feedstock, catalyst, monolithic reactor, and supercritical fluid technology , 2016 .

[117]  Cynthia Ebert,et al.  Efficient immobilisation of industrial biocatalysts: criteria and constraints for the selection of organic polymeric carriers and immobilisation methods. , 2013, Chemical Society reviews.

[118]  Nicholas J. Turner,et al.  Combined Imine Reductase and Amine Oxidase Catalyzed Deracemization of Nitrogen Heterocycles , 2016 .

[119]  R. Sheldon,et al.  Cross-linked enzyme aggregates: a simple and effective method for the immobilization of penicillin acylase. , 2000, Organic letters.

[120]  R. Sheldon,et al.  A green, fully enzymatic procedure for amine resolution, using a lipase and a penicillin G acylase , 2008 .

[121]  R. Houghten General method for the rapid solid-phase synthesis of large numbers of peptides: specificity of antigen-antibody interaction at the level of individual amino acids. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[122]  Joerg H. Schrittwieser,et al.  Multi-Enzymatic Cascade Reactions: Overview and Perspectives , 2011 .

[123]  B. Adger Industrial synthesis of optically active compounds , 1995 .

[124]  D. Murzin,et al.  Heterogeneous Chemoenzymatic Catalyst Combinations for One‐Pot Dynamic Kinetic Resolution Applications , 2015 .

[125]  A. Klibanov Asymmetric transformations catalyzed by enzymes in organic solvents , 1990 .

[126]  William H Green,et al.  Minimizing E-factor in the continuous-flow synthesis of diazepam and atropine. , 2017, Bioorganic & medicinal chemistry.

[127]  John M Woodley,et al.  Microbial biocatalytic processes and their development. , 2006, Advances in applied microbiology.

[128]  Claudia Schmidt-Dannert,et al.  Multi-enzymatic synthesis. , 2010, Current opinion in chemical biology.

[129]  E. Favela-Torres,et al.  Cross-linked enzyme aggregates (CLEA) in enzyme improvement – a review , 2016 .

[130]  M. Navia,et al.  Protein Crystals as Novel Catalytic Materials. , 2001, Angewandte Chemie.

[131]  Yonghua Wang,et al.  Enzymatic selective synthesis of 1,3-DAG based on deep eutectic solvent acting as substrate and solvent , 2015, Bioprocess and Biosystems Engineering.

[132]  P. Poechlauer,et al.  Continuous Processing in the Manufacture of Active Pharmaceutical Ingredients and Finished Dosage Forms: An Industry Perspective , 2012 .

[133]  S. Ansari,et al.  Potential applications of enzymes immobilized on/in nano materials: A review. , 2012, Biotechnology advances.

[134]  Frances H Arnold,et al.  Expanding the enzyme universe: accessing non-natural reactions by mechanism-guided directed evolution. , 2015, Angewandte Chemie.

[135]  S. Al-Athel,et al.  Report of the World Commission on Environment and Development: "Our Common Future" , 1987 .

[136]  Christopher Hardacre,et al.  Catalysis in ionic liquids. , 2007, Chemical reviews.

[137]  J. Woodley,et al.  A Rapid Selection Procedure for Simple Commercial Implementation of ω-Transaminase Reactions , 2016 .

[138]  A. Jana,et al.  Immobilization of amyloglucosidase from SSF of Aspergillus niger by crosslinked enzyme aggregate onto magnetic nanoparticles using minimum amount of carrier and characterizations , 2013 .

[139]  H. H. Beeftink,et al.  In situ product removal during enzymatic cephalexin synthesis by complexation , 2002 .

[140]  Linqiu Cao,et al.  Enzyme immobilisation: fundamentals and application. , 2013, Chemical Society reviews.

[141]  Bernhard Hauer,et al.  Industrial methods for the production of optically active intermediates. , 2004, Angewandte Chemie.

[142]  K. Khorshidi,et al.  Preparation and characterization of nanomagnetic cross-linked cellulase aggregates for cellulose bioconversion , 2016 .

[143]  J. Hallett,et al.  Deconstruction of lignocellulosic biomass with ionic liquids , 2013 .

[144]  Concepción Jiménez-González,et al.  The evolution of life cycle assessment in pharmaceutical and chemical applications – a perspective , 2014 .

[145]  Denise Ott,et al.  Rules and benefits of Life Cycle Assessment in green chemical process and synthesis design: a tutorial review , 2015 .

[146]  Frances H Arnold,et al.  Directed enzyme evolution: climbing fitness peaks one amino acid at a time. , 2009, Current opinion in chemical biology.

[147]  S. M. Glueck,et al.  Development and Scaling-Up of the Fragrance Compound 4-Ethylguaiacol Synthesis via a Two-Step Chemo-Enzymatic Reaction Sequence , 2017 .

[148]  Wolfgang Kroutil,et al.  Continuous flow synthesis of chiral amines in organic solvents: immobilization of E. coli cells containing both ω-transaminase and PLP. , 2014, Organic letters.

[149]  Rafiqul Gani,et al.  Phenomena Based Methodology for Process Synthesis Incorporating Process Intensification , 2013 .

[150]  D. Brady,et al.  Practical Methods for Biocatalysis and Biotransformations 2: Whittall/Practical Methods for Biocatalysis and Biotransformations 2 , 2012 .

[151]  Xiao‐Qi Yu,et al.  Surfactant-activated magnetic cross-linked enzyme aggregates (magnetic CLEAs) of Thermomyces lanuginosus lipase for biodiesel production , 2015 .

[152]  F. Arnold,et al.  Directed evolution of cytochrome c for carbon–silicon bond formation: Bringing silicon to life , 2016, Science.

[153]  G J Lye,et al.  Application of in situ product-removal techniques to biocatalytic processes. , 1999, Trends in biotechnology.

[154]  W. Kopp,et al.  Easily handling penicillin G acylase magnetic cross-linked enzymes aggregates: Catalytic and morphological studies , 2014 .

[155]  John M. Woodley,et al.  Process Requirements of Galactose Oxidase Catalyzed Oxidation of Alcohols , 2015 .

[156]  Roger A. Sheldon,et al.  Continuous kinetic resolution catalysed by cross-linked enzyme aggregates, ‘CLEAs’, in supercritical CO2 , 2006 .

[157]  Cheng-Kang Lee,et al.  Biocatalytic reactions in hydrophobic ionic liquids , 2009 .

[158]  G. Antranikian,et al.  Practical application of different enzymes immobilized on sepabeads , 2008, Bioprocess and biosystems engineering.

[159]  Julie B. Zimmerman,et al.  Designing nanomaterials to maximize performance and minimize undesirable implications guided by the Principles of Green Chemistry. , 2015, Chemical Society reviews.

[160]  Hua Zhao,et al.  Lipase dissolution and stabilization in ether-functionalized ionic liquids , 2009 .

[161]  R. Sheldon,et al.  Biocatalysis in ionic liquids. , 2007, Chemical reviews.

[162]  Nitin W. Fadnavis,et al.  Efficient Immobilization of Lecitase in Gelatin Hydrogel and Degumming of Rice Bran Oil Using a Spinning Basket Reactor , 2008 .

[163]  Rohana Abu,et al.  Application of Enzyme Coupling Reactions to Shift Thermodynamically Limited Biocatalytic Reactions , 2015 .

[164]  J. Woodley,et al.  Application of NAD(P)H oxidase for cofactor regeneration in dehydrogenase catalyzed oxidations , 2016 .

[165]  John M. Woodley,et al.  Future directions for in‐situ product removal (ISPR) , 2008 .

[166]  Peter Saling,et al.  Assessing the Environmental-Hazard Potential for Life Cycle Assessment, Eco-Efficiency and SEEbalance (8 pp) , 2005 .

[167]  Lawrence X. Yu,et al.  Modernizing Pharmaceutical Manufacturing: from Batch to Continuous Production , 2015, Journal of Pharmaceutical Innovation.

[168]  H. Steinrück,et al.  Ionic Liquids in Catalysis , 2015, Catalysis Letters.

[169]  V. Pârvulescu,et al.  Biocatalytic epoxidation of α-pinene to oxy-derivatives over cross-linked lipase aggregates , 2016 .

[170]  E. Balskus,et al.  Opportunities for merging chemical and biological synthesis. , 2014, Current opinion in biotechnology.

[171]  M. Tabatabaei,et al.  Immobilization of cellulase enzyme on superparamagnetic nanoparticles and determination of its activity and stability , 2011 .

[172]  Isabelle Migneault,et al.  Glutaraldehyde: behavior in aqueous solution, reaction with proteins, and application to enzyme crosslinking. , 2004, BioTechniques.

[173]  Mary Ann Curran,et al.  Life Cycle Assessment: a review of the methodology and its application to sustainability , 2013 .

[174]  Roger A Sheldon,et al.  E factors, green chemistry and catalysis: an odyssey. , 2008, Chemical communications.

[175]  I. Arends,et al.  Are Natural Deep Eutectic Solvents the Missing Link in Understanding Cellular Metabolism and Physiology?[W] , 2011, Plant Physiology.

[176]  E. Magner Immobilisation of enzymes on mesoporous silicate materials. , 2013, Chemical Society reviews.

[177]  John M. Woodley,et al.  PEER REVIEW ORIGINAL RESEARCH: EHS & LCA assessment for 7-ACA synthesis A case study for comparing biocatalytic & chemical synthesis , 2008 .

[178]  James H. Clark,et al.  Towards a holistic approach to metrics for the 21st century pharmaceutical industry , 2015 .

[179]  Volker Sieber,et al.  Cell-free metabolic engineering: production of chemicals by minimized reaction cascades. , 2012, ChemSusChem.

[180]  Andreas Vogel,et al.  Expanding the range of substrate acceptance of enzymes: combinatorial active-site saturation test. , 2005, Angewandte Chemie.

[181]  V. Sewalt,et al.  The Generally Recognized as Safe (GRAS) Process for Industrial Microbial Enzymes , 2016 .

[182]  H. Cabana,et al.  Towards high potential magnetic biocatalysts for on-demand elimination of pharmaceuticals. , 2016, Bioresource technology.

[183]  Roger A. Sheldon,et al.  Synthesis of enantiomerically pure (S)-mandelic acid using an oxynitrilase–nitrilase bienzymatic cascade: a nitrilase surprisingly shows nitrile hydratase activity , 2006 .

[184]  Dominique M. Roberge,et al.  From Batch to Continuous Chemical Synthesis—A Toolbox Approach , 2014 .

[185]  Roger A. Sheldon,et al.  Atom utilisation, E factors and the catalytic solution , 2000 .

[186]  Paul N. Devine,et al.  Biocatalytic Asymmetric Synthesis of Chiral Amines from Ketones Applied to Sitagliptin Manufacture , 2010, Science.

[187]  N. Gathergood,et al.  Biodegradation studies of ionic liquids. , 2010, Chemical Society reviews.

[188]  A. Stolz,et al.  Enzymatic cascade synthesis of (S)-2-hydroxycarboxylic amides and acids: Cascade reactions employing a hydroxynitrile lyase, nitrile-converting enzymes and an amidase , 2015 .

[189]  Rafiqul Gani,et al.  Model-based design and analysis of glucose isomerization process operation , 2017, Comput. Chem. Eng..

[190]  Marco Eissen,et al.  Environmental performance metrics for daily use in synthetic chemistry. , 2002, Chemistry.

[191]  R. Codd,et al.  Reverse Biosynthesis: Generating Combinatorial Pools of Drug Leads from Enzyme‐Mediated Fragmentation of Natural Products , 2017, Chembiochem : a European journal of chemical biology.

[192]  Frances H Arnold,et al.  Chemomimetic biocatalysis: exploiting the synthetic potential of cofactor-dependent enzymes to create new catalysts. , 2015, Journal of the American Chemical Society.

[193]  Michel Cabassud,et al.  Optimisation of solvent replacement procedures according to economic and environmental criteria , 2006 .

[194]  Huimin Zhao,et al.  Improving and repurposing biocatalysts via directed evolution. , 2015, Current opinion in chemical biology.

[195]  C. Wittmann,et al.  Top value platform chemicals: bio-based production of organic acids. , 2015, Current opinion in biotechnology.

[196]  H. P. Cady THE CHEMISTRY OF THE FUTURE. , 1927, Science.

[197]  Chul-Woong Cho,et al.  Environmental fate and toxicity of ionic liquids: a review. , 2010, Water research.

[198]  Helene Olivier-Bourbigou,et al.  Ionic liquids and catalysis: Recent progress from knowledge to applications , 2010 .

[199]  R. Sheldon,et al.  Epoxidation and Baeyer–Villiger oxidation using hydrogen peroxide and a lipase dissolved in ionic liquids , 2011 .

[200]  R. Sheldon,et al.  Lipase-catalyzed transformations with unnatural acyl acceptors , 1994 .

[201]  Andreas S Bommarius,et al.  Status of protein engineering for biocatalysts: how to design an industrially useful biocatalyst. , 2011, Current opinion in chemical biology.

[202]  A. Klibanov Why are enzymes less active in organic solvents than in water? , 1997, Trends in biotechnology.

[203]  A. Bruggink Synthesis of β-Lactam antibiotics : chemistry, biocatalysis & process integration , 2001 .

[204]  R. Sheldon,et al.  Dynamic kinetic resolution of phenylglycine esters via lipase-catalysed ammonolysis , 1999 .

[205]  H. Xu,et al.  Insights into the impact of deep eutectic solvents on horseradish peroxidase: Activity, stability and structure , 2014 .

[206]  Ronny Martínez,et al.  Reengineering CelA2 cellulase for hydrolysis in aqueous solutions of deep eutectic solvents and concentrated seawater , 2012 .

[207]  B. G. Hermann,et al.  Today’s and tomorrow’s bio-based bulk chemicals from white biotechnology , 2007, Applied biochemistry and biotechnology.

[208]  C. Afonso,et al.  Impact of ionic liquids in environment and humans: An overview , 2010, Human & experimental toxicology.

[209]  Fuan Wu,et al.  Microfluidic biocatalysis enhances the esterification of caffeic acid and methanol under continuous‐flow conditions , 2016 .

[210]  L. Giver,et al.  Engineered enzymes for chemical production. , 2008, Biotechnology and bioengineering.

[211]  Xue Han,et al.  Continuous reactions in supercritical carbon dioxide: problems, solutions and possible ways forward. , 2012, Chemical Society reviews.

[212]  Hans Iding,et al.  Identification of (S)-selective transaminases for the asymmetric synthesis of bulky chiral amines. , 2016, Nature chemistry.

[213]  Lin Li,et al.  Preparation of Cross-Linked Cellulase Aggregates onto Magnetic Chitosan Microspheres , 2012 .

[214]  C. Hutchison,et al.  Mutagenesis at a specific position in a DNA sequence. , 1978, The Journal of biological chemistry.

[215]  Lorna J. Hepworth,et al.  Constructing Biocatalytic Cascades: In Vitro and in Vivo Approaches to de Novo Multi-Enzyme Pathways , 2017 .

[216]  Y. Miao,et al.  Recent developments in enzyme promiscuity for carbon-carbon bond-forming reactions. , 2015, Current opinion in chemical biology.

[217]  J. Cui,et al.  Hybrid Magnetic Cross-Linked Enzyme Aggregates of Phenylalanine Ammonia Lyase from Rhodotorula glutinis , 2014, PloS one.

[218]  Paul A Wender,et al.  Function-oriented synthesis, step economy, and drug design. , 2008, Accounts of chemical research.

[219]  R. Souza,et al.  Towards a continuous flow environment for lipase-catalyzed reactions , 2013 .

[220]  P. D. D. María,et al.  Enzymatic deglycosylation of flavonoids in deep eutectic solvents-aqueous mixtures: paving the way for sustainable flavonoid chemistry , 2016 .

[221]  S. Handy,et al.  Towards the Ideal Synthesis , 1998 .

[222]  Frances H. Arnold,et al.  Olefin Cyclopropanation via Carbene Transfer Catalyzed by Engineered Cytochrome P450 Enzymes , 2013, Science.

[223]  G. Baker,et al.  Designing enzyme-compatible ionic liquids that can dissolve carbohydrates , 2008 .

[224]  R. Sheldon,et al.  A four-step enzymatic cascade for the one-pot synthesis of non-natural carbohydrates from glycerol. , 2000, The Journal of organic chemistry.

[225]  C. Chiappe,et al.  Ionic green solvents from renewable resources , 2007 .

[226]  P. D. D. María,et al.  Highly enantioselective tandem enzyme–organocatalyst crossed aldol reactions with acetaldehyde in deep-eutectic-solvents , 2014 .

[227]  Jason P. Jordan,et al.  Preparation and characterization of cellulase-bound magnetite nanoparticles , 2011 .

[228]  L. Leseurre,et al.  Eco-footprint: a new tool for the “Made in Chimex” considered approach , 2014 .

[229]  H. Cabana,et al.  Laccase immobilization and insolubilization: from fundamentals to applications for the elimination of emerging contaminants in wastewater treatment , 2013, Critical reviews in biotechnology.

[230]  John M. Woodley,et al.  Bioprocess intensification for the effective production of chemical products , 2017, Comput. Chem. Eng..

[231]  François Jérôme,et al.  Deep eutectic solvents: syntheses, properties and applications. , 2012, Chemical Society reviews.

[232]  N. Budisa,et al.  Supercritical Carbon Dioxide and Its Potential as a Life-Sustaining Solvent in a Planetary Environment , 2014, Life.

[233]  W. Leitner,et al.  Biocatalysis in ionic liquids: batchwise and continuous flow processes using supercritical carbon dioxide as the mobile phase. , 2002, Chemical communications.

[234]  Ana Cauerhff,et al.  Recent trends in biocatalysis engineering. , 2012, Bioresource technology.

[235]  Concepción Jiménez-González,et al.  Using the Right Green Yardstick: Why Process Mass Intensity Is Used in the Pharmaceutical Industry To Drive More Sustainable Processes , 2011 .

[236]  Hafiz M.N. Iqbal,et al.  Recent trends and valorization of immobilization strategies and ligninolytic enzymes by industrial biotechnology , 2014 .

[237]  Roger A. Sheldon,et al.  Introduction: Green Chemistry and Catalysis , 2007 .

[238]  P. Roy,et al.  Industrial Synthesis of Semisynthetic Antibiotics , 2001 .

[239]  Rafiqul Gani,et al.  Process intensification: A perspective on process synthesis , 2010 .

[240]  Roger A. Sheldon,et al.  The E factor 25 years on: the rise of green chemistry and sustainability , 2017 .

[241]  Peter H Seeberger,et al.  Applying flow chemistry: methods, materials, and multistep synthesis. , 2013, The Journal of organic chemistry.

[242]  Andreas S Bommarius,et al.  Biocatalysis: A Status Report. , 2015, Annual review of chemical and biomolecular engineering.

[243]  Walter Klöpffer,et al.  Background and Future Prospects in Life Cycle Assessment , 2014 .

[244]  N. Turner,et al.  Comparison of a Batch and Flow Approach for the Lipase-Catalyzed Resolution of a Cyclopropanecarboxylate Ester, A Key Building Block for the Synthesis of Ticagrelor , 2017 .

[245]  Manfred T. Reetz,et al.  Creation of Enantioselective Biocatalysts for Organic Chemistry by In Vitro Evolution , 1997 .

[246]  Alan D. Curzons,et al.  So you think your process is green, how do you know?—Using principles of sustainability to determine what is green–a corporate perspective , 2001 .

[247]  Diego A. Alonso,et al.  Deep Eutectic Solvents: The Organic Reaction Medium of the Century , 2016 .

[248]  J. Qiu,et al.  Preparation of Magnetic Chitosan Nanoparticles As Support for Cellulase Immobilization , 2014 .

[249]  P. Gallezot,et al.  Conversion of biomass to selected chemical products. , 2012, Chemical Society reviews.

[250]  S. Berensmeier,et al.  Immobilization of Cellulase on Magnetic Nanocarriers , 2016, ChemistryOpen.

[251]  Roger A Sheldon,et al.  Biocatalysis and Biomass Conversion in Alternative Reaction Media. , 2016, Chemistry.

[252]  Xianfu Lin,et al.  Enzymatic Promiscuity for Organic Synthesis and Cascade Process , 2010 .

[253]  John Whittall,et al.  Practical methods for biocatalysis and biotransformations , 2009 .

[254]  A. Polydera,et al.  Deep Eutectic Solvents as Media for Peroxidation Reactions Catalyzed by Heme-Dependent Biocatalysts , 2016 .

[255]  Shang-Tian Yang,et al.  Bioprocessing technologies in biorefinery for sustainable production of fuels, chemicals, and polymers , 2013 .

[256]  Roger A. Sheldon,et al.  Enzyme Immobilization: The Quest for Optimum Performance , 2007 .

[257]  R. Sheldon,et al.  Lipase-catalyzed reactions in ionic liquids. , 2000, Organic letters.

[258]  M. Lilly,et al.  Process design for the oxidation of fluorobenzene to fluorocatechol by Pseudomonas putida , 1997 .

[259]  Michel Vaultier,et al.  Continuous green biocatalytic processes using ionic liquids and supercritical carbon dioxide. , 2002, Chemical communications.

[260]  P. D. D. María,et al.  Medium and reaction engineering for the establishment of a chemo-enzymatic dynamic kinetic resolution of rac-benzoin in batch and continuous mode , 2015 .

[261]  Roberto A Chica,et al.  Semi-rational approaches to engineering enzyme activity: combining the benefits of directed evolution and rational design. , 2005, Current opinion in biotechnology.

[262]  Shamraja S. Nadar,et al.  Carrier free co-immobilization of alpha amylase, glucoamylase and pullulanase as combined cross-linked enzyme aggregates (combi-CLEAs): a tri-enzyme biocatalyst with one pot starch hydrolytic activity. , 2013, Bioresource technology.

[263]  F. Péter,et al.  An Integrated Process of Ionic Liquid Pretreatment and Enzymatic Hydrolysis of Lignocellulosic Biomass with Immobilised Cellulase , 2014 .

[264]  Sze-Wing Wong,et al.  Model Driven Process Design and Development for a Continuous Process , 2014 .

[265]  M. Reetz,et al.  Biocatalysis in organic chemistry and biotechnology: past, present, and future. , 2013, Journal of the American Chemical Society.

[266]  Roger A. Sheldon,et al.  Overcoming barriers to green chemistry in the pharmaceutical industry – the Green Aspiration Level™ concept , 2015 .

[267]  E. Sakai,et al.  Increase in stability of cellulase immobilized on functionalized magnetic nanospheres , 2015 .

[268]  R. Sheldon CATALYSIS AND POLLUTION PREVENTION , 1997 .

[269]  S. Y. Wong,et al.  On-demand continuous-flow production of pharmaceuticals in a compact, reconfigurable system , 2016, Science.

[270]  Jack Liang,et al.  Highly Enantioselective Reduction of a Small Heterocyclic Ketone: Biocatalytic Reduction of Tetrahydrothiophene-3-one to the Corresponding (R)-Alcohol , 2010 .

[271]  U. Bornscheuer,et al.  7.22 Enzyme Catalytic Promiscuity: Expanding the Catalytic Action of Enzymes to New Reactions , 2012 .

[272]  S. Hosseini,et al.  Palladium nanoparticles supported on Fe3O4/amino acid nanocomposite: Highly active magnetic catalyst for solvent-free aerobic oxidation of alcohols , 2014 .

[273]  J. D. Taylor,et al.  Continuous steam explosion , 1995 .

[274]  R. Kazlauskas,et al.  Improved preparation and use of room-temperature ionic liquids in lipase-catalyzed enantio- and regioselective acylations. , 2001, The Journal of organic chemistry.

[275]  Z. Findrik,et al.  Biotransformation of D‐methionine into L‐methionine in the cascade of four enzymes , 2007, Biotechnology and bioengineering.

[276]  C. López,et al.  Magnetic Cross-Linked Enzyme Aggregates (mCLEAs) of Candida antarctica Lipase: An Efficient and Stable Biocatalyst for Biodiesel Synthesis , 2014, PloS one.

[277]  Frances H Arnold,et al.  Improved cyclopropanation activity of histidine-ligated cytochrome P450 enables the enantioselective formal synthesis of levomilnacipran. , 2014, Angewandte Chemie.

[278]  Shamraja S. Nadar,et al.  Carrier free co-immobilization of glucoamylase and pullulanase as combi-cross linked enzyme aggregates (combi-CLEAs) , 2013 .

[279]  Jean Mane,et al.  GREEN MOTION: a new and easy to use green chemistry metric from laboratories to industry , 2015 .

[280]  X. Hou,et al.  Evaluation of Toxicity and Biodegradability of Cholinium Amino Acids Ionic Liquids , 2013, PloS one.

[281]  B. Bhanage,et al.  Applications of ionic liquids in organic synthesis and catalysis , 2014, Clean Technologies and Environmental Policy.

[282]  Wolfgang Kroutil,et al.  Artificial multi-enzyme networks for the asymmetric amination of sec-alcohols. , 2013, Chemistry.

[283]  R. Rodrigues,et al.  Preparation and characterization of a Combi-CLEAs from pectinases and cellulases: a potential biocatalyst for grape juice clarification , 2016 .

[284]  Lara Babich,et al.  Synthesis of carbohydrates in a continuous flow reactor by immobilized phosphatase and aldolase. , 2012, ChemSusChem.

[285]  John M. Woodley,et al.  In Situ Product Removal as a Tool for Bioprocessing , 1993, Bio/Technology.

[286]  R. Parthasarathi,et al.  Design of low-cost ionic liquids for lignocellulosic biomass pretreatment , 2015 .

[287]  M. Bozorgmehr,et al.  How a protein can remain stable in a solvent with high content of urea: insights from molecular dynamics simulation of Candida antarctica lipase B in urea : choline chloride deep eutectic solvent. , 2014, Physical chemistry chemical physics : PCCP.

[288]  Ian R. Baxendale,et al.  The Use of Gases in Flow Synthesis , 2016 .

[289]  Manfred T Reetz,et al.  Directed evolution of enantioselective enzymes: an unconventional approach to asymmetric catalysis in organic chemistry. , 2009, The Journal of organic chemistry.

[290]  T. Graedel Green Chemistry and Sustainable Development , 2007 .

[291]  Sergio Riva,et al.  Role of solvents in the control of enzyme selectivity in organic media , 1995 .

[292]  J. Reith,et al.  Ethanol-based organosolv fractionation of wheat straw for the production of lignin and enzymatically digestible cellulose. , 2013, Bioresource technology.

[293]  R. Sheldon,et al.  Lipase-catalysed ammoniolysis of lipids. A facile synthesis of fatty acid amides , 1996 .

[294]  Lutz Hilterhaus,et al.  Reactor Concept for Lipase-Catalyzed Solvent-Free Conversion of Highly Viscous Reactants Forming Two-Phase Systems , 2008 .

[295]  F. Arnold,et al.  Tuning the activity of an enzyme for unusual environments: sequential random mutagenesis of subtilisin E for catalysis in dimethylformamide. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[296]  Maggel Deetlefs,et al.  Assessing the greenness of some typical laboratory ionic liquid preparations , 2010 .

[297]  P. Dalby,et al.  Identification and use of an alkane transporter plug-in for applications in biocatalysis and whole-cell biosensing of alkanes , 2014, Scientific Reports.

[298]  J. Keasling,et al.  Engineering Cellular Metabolism , 2016, Cell.

[299]  Sergio Riva,et al.  Organic synthesis with enzymes in non-aqueous media , 2008 .

[300]  Luc Patiny,et al.  Beilstein Journal of Organic Chemistry Beilstein Journal of Organic Chemistry Beilstein Journal of Organic Chemistry Ecoscale, a Semi-quantitative Tool to Select an Organic Preparation Based on Economical and Ecological Parameters , 2022 .

[301]  C. Dumon,et al.  White biotechnology: State of the art strategies for the development of biocatalysts for biorefining. , 2015, Biotechnology advances.

[302]  M. Zmijewski,et al.  Large-scale stereoselective enzymatic ketone reduction with in situ product removal via polymeric adsorbent resins , 1997 .

[303]  Oliver May,et al.  Biocatalytic reductions: from lab curiosity to "first choice". , 2007, Accounts of chemical research.

[304]  H. Ohno,et al.  Bio ionic liquids: room temperature ionic liquids composed wholly of biomaterials , 2007 .

[305]  W. Stemmer Rapid evolution of a protein in vitro by DNA shuffling , 1994, Nature.

[306]  B. Trost,et al.  The atom economy--a search for synthetic efficiency. , 1991, Science.

[307]  Zhoutong Sun,et al.  Whole-Cell-Catalyzed Multiple Regio- and Stereoselective Functionalizations in Cascade Reactions Enabled by Directed Evolution. , 2016, Angewandte Chemie.

[308]  A. Klibanov,et al.  Enzymatic production of high fructose corn syrup (HFCS) containing 55% fructose in aqueous ethanol. , 1987, Biotechnology and bioengineering.

[309]  Pablo Domínguez de María,et al.  Novel choline-chloride-based deep-eutectic-solvents with renewable hydrogen bond donors: levulinic acid and sugar-based polyols , 2012 .

[310]  Reinu E. Abraham,et al.  Suitability of magnetic nanoparticle immobilised cellulases in enhancing enzymatic saccharification of pretreated hemp biomass , 2014, Biotechnology for Biofuels.

[311]  István T. Horváth,et al.  Valorization of Biomass: Deriving More Value from Waste , 2012, Science.

[312]  John H. Grate,et al.  A green-by-design biocatalytic process for atorvastatin intermediate , 2010 .

[313]  R. Sheldon Green and sustainable manufacture of chemicals from biomass: state of the art , 2014 .

[314]  V. Rathod,et al.  Magnetic macromolecular cross linked enzyme aggregates (CLEAs) of glucoamylase. , 2016, Enzyme and microbial technology.

[315]  M. Potdar,et al.  Recent Developments in Chemical Synthesis with Biocatalysts in Ionic Liquids , 2015, Molecules.

[316]  L. Rossi,et al.  Magnetic nanomaterials in catalysis: advanced catalysts for magnetic separation and beyond , 2014 .

[317]  N. Bruce,et al.  Cofactor-dependent enzyme catalysis in functionalized ionic solvents. , 2004, Chemical communications.

[318]  Thomas E. Graedel,et al.  Green Chemistry in an industrial ecology context , 1999 .

[319]  D. Kell,et al.  Membrane transporter engineering in industrial biotechnology and whole cell biocatalysis. , 2015, Trends in biotechnology.

[320]  R. Sheldon,et al.  Fully Enzymatic Resolution of Chiral Amines: Acylation and Deacylation in the Presence of Candida antarctica Lipase B , 2008 .

[321]  Brett I. Pletschke,et al.  Strategic optimization of xylanase–mannanase combi-CLEAs for synergistic and efficient hydrolysis of complex lignocellulosic substrates , 2015 .

[322]  John M Woodley,et al.  Characterization of a continuous agitated cell reactor for oxygen dependent biocatalysis , 2017, Biotechnology and bioengineering.

[323]  Nicholas J Turner,et al.  Directed evolution drives the next generation of biocatalysts. , 2009, Nature chemical biology.

[324]  Ángel Berenguer-Murcia,et al.  Potential of Different Enzyme Immobilization Strategies to Improve Enzyme Performance , 2011 .

[325]  P. Villeneuve,et al.  Evaluation of deep eutectic solvents as new media for Candida antarctica B lipase catalyzed reactions , 2012 .

[326]  C. Pretti,et al.  Acute toxicity of ionic liquids for three freshwater organisms: Pseudokirchneriella subcapitata, Daphnia magna and Danio rerio. , 2009, Ecotoxicology and environmental safety.

[327]  Rui L. Reis,et al.  Natural Deep Eutectic Solvents – Solvents for the 21st Century , 2014 .

[328]  Ning Li,et al.  Enhancing the activity and regioselectivity of lipases for 3'-benzoylation of floxuridine and its analogs by using ionic liquid-containing systems. , 2008, Journal of biotechnology.

[329]  Kun Dong,et al.  Biodegradable naphthenic acid ionic liquids: synthesis, characterization, and quantitative structure-biodegradation relationship. , 2008, Chemistry.

[330]  Krist V. Gernaey,et al.  Multienzyme-Catalyzed Processes: Next-Generation Biocatalysis , 2011 .

[331]  A. Bruggink Synthesis of β-Lactam Antibiotics , 2001 .

[332]  J. Kennedy,et al.  Immobilization of Enzymes and Cells , 2006, Methods in Biotechnology™.

[333]  Roger M. Howard,et al.  Pseudomonas stutzeri lipase: a useful biocatalyst for aminolysis reactions , 2011 .

[334]  Klavs F. Jensen,et al.  Mass Transport and Reactions in the Tube-in-Tube Reactor , 2013 .

[335]  J. Nielsen,et al.  Biobased organic acids production by metabolically engineered microorganisms. , 2016, Current opinion in biotechnology.

[336]  John M. Woodley,et al.  Life cycle assessment in green chemistry: overview of key parameters and methodological concerns , 2013, The International Journal of Life Cycle Assessment.

[337]  Roger A Sheldon,et al.  Immobilised enzymes: carrier-bound or carrier-free? , 2003, Current opinion in biotechnology.

[338]  F. Arnold,et al.  Highly Stereoselective Biocatalytic Synthesis of Key Cyclopropane Intermediate to Ticagrelor. , 2016, ACS catalysis.

[339]  T. Matsuda,et al.  Liquid carbon dioxide as an effective solvent for immobilized Candida antarctica lipase B catalyzed transesterification , 2015 .

[340]  John M Woodley,et al.  Protein engineering of enzymes for process applications. , 2013, Current opinion in chemical biology.

[341]  T. Ikariya,et al.  Asymmetric synthesis using hydrolytic enzymes in supercritical carbon dioxide , 2005 .

[342]  H. H. Yiu,et al.  Enzyme–magnetic nanoparticle hybrids: new effective catalysts for the production of high value chemicals , 2012 .

[343]  N. Kockmann,et al.  Microreactor Technology and Continuous Processes in the Fine Chemical and Pharmaceutical Industry: Is the Revolution Underway? , 2008 .

[344]  A. Marra,et al.  Synthesis and applications of ionic liquids derived from natural sugars. , 2011, Topics in current chemistry.

[345]  Volker Hessel,et al.  Novel process windows for enabling, accelerating, and uplifting flow chemistry. , 2013, ChemSusChem.

[346]  N. Turner,et al.  Biocatalytic retrosynthesis. , 2013, Nature chemical biology.

[347]  J. Kennedy,et al.  Use of immobilised biocatalysts in the processing of cheese whey. , 2009, International journal of biological macromolecules.

[348]  Roger A. Sheldon,et al.  Ester ammoniolysis: a new enzymatic reaction , 1993 .

[349]  Jesús Martín,et al.  Selective esterification of phthalic acids in two ionic liquids at high temperatures using a thermostable lipase of Bacillus thermocatenulatus: A comparative study , 2008 .

[350]  Thomas Grotkjær,et al.  Commercial Development of Fermentation Processes , 2015 .

[351]  San Kiang,et al.  Model-Based Solvent Selection during Conceptual Process Design of a New Drug Manufacturing Process , 2009 .

[352]  John M. Woodley,et al.  A future perspective on the role of industrial biotechnology for chemicals production , 2013 .

[353]  Masahiro Yoshizawa,et al.  Room temperature ionic liquids from 20 natural amino acids. , 2005, Journal of the American Chemical Society.

[354]  Roger A Sheldon,et al.  Enzyme immobilisation in biocatalysis: why, what and how. , 2013, Chemical Society reviews.

[355]  Roger A. Sheldon,et al.  Synthesis of Aliphatic (S)-α-Hydroxycarboxylic Amides using a One-Pot Bienzymatic Cascade of Immobilised Oxynitrilase and Nitrile Hydratase , 2009 .

[356]  R. Sheldon CHAPTER 9:Ionic Liquids in the Biorefinery: How Green and Sustainable Are They? , 2015 .

[357]  Roger A. Sheldon,et al.  CONSIDER THE ENVIRONMENTAL QUOTIENT , 1994 .

[358]  Albrecht Berkessel,et al.  Combination of Asymmetric Organo- and Biocatalytic Reactions in Organic Media Using Immobilized Catalysts in Different Compartments , 2014 .

[359]  Roger A. Sheldon,et al.  The combi-CLEA approach: enzymatic cascade synthesis of enantiomerically pure (S)-mandelic acid , 2013 .

[360]  F. Hernández‐Fernández,et al.  Biocatalytic ester synthesis in ionic liquid media , 2010 .

[361]  Ed Jones,et al.  Scaling Up Biocatalysis Reactions in Flow Reactors , 2012 .

[362]  E. García‐Verdugo,et al.  Supported Ionic Liquid-Like Phases (SILLPs) for enzymatic processes: Continuous KR and DKR in SILLP–scCO2 systems , 2010 .

[363]  Yongzhong Wang,et al.  Co-expression of the recombined alcohol dehydrogenase and glucose dehydrogenase and cross-linked enzyme aggregates stabilization. , 2017, Bioresource technology.

[364]  A. Illanes,et al.  Aroma Release in Wine Using Co-Immobilized Enzyme Aggregates , 2016, Molecules.

[365]  Dongzhi Wei,et al.  Combined cross-linked enzyme aggregates (combi-CLEAs) for efficient integration of a ketoreductase and a cofactor regeneration system. , 2014, Journal of biotechnology.

[366]  Y. Marcus Deep Eutectic Solvents , 2018 .

[367]  Bernhard Hauer,et al.  New generation of biocatalysts for organic synthesis. , 2014, Angewandte Chemie.

[368]  Tomoko Matsuda,et al.  Recent progress in biocatalysis using supercritical carbon dioxide. , 2013, Journal of bioscience and bioengineering.

[369]  Lucie A. Pfaltzgraff,et al.  Food waste biomass: a resource for high-value chemicals , 2013 .

[370]  C. Wiles,et al.  Continuous flow reactors: a perspective , 2012 .

[371]  C. Roessner,et al.  Genetically engineered synthesis of precorrin-6x and the complete corrinoid, hydrogenobyrinic acid, an advanced precursor of vitamin B12. , 1994, Chemistry & biology.

[372]  J. Mcauliffe,et al.  Industrial Use of Immobilized Enzymes , 2013 .

[373]  Roger A Sheldon,et al.  Biocatalysis engineering: the big picture. , 2017, Chemical Society reviews.

[374]  Wolfgang Kroutil,et al.  Recent biocatalytic oxidation–reduction cascades , 2011, Current opinion in chemical biology.

[375]  Pilar Hoyos,et al.  Biocatalysis in the Pharmaceutical Industry. A Greener Future , 2013 .

[376]  A. Klibanov,et al.  Enzymatic catalysis in organic media at 100 degrees C. , 1984, Science.

[377]  Junhua Tao,et al.  Biocatalysis in development of green pharmaceutical processes. , 2009, Current opinion in chemical biology.

[378]  Ronald L. Crawford,et al.  Novel method for immobilization of enzymes to magnetic nanoparticles , 2008 .

[379]  Marina Cvjetko Bubalo,et al.  Cholinium-based deep eutectic solvents and ionic liquids for lipase-catalyzed synthesis of butyl acetate , 2015 .

[380]  R. Xiao,et al.  Redesigning alcohol dehydrogenases/reductases for more efficient biosynthesis of enantiopure isomers. , 2015, Biotechnology advances.

[381]  R. Sheldon Enzyme‐Catalyzed Cascade Reactions , 2008 .

[382]  Gregory Hughes,et al.  Development of an Immobilized Transaminase Capable of Operating in Organic Solvent , 2012 .

[383]  R. Sheldon,et al.  Nitrile hydratase CLEAs: The immobilization and stabilization of an industrially important enzyme , 2008 .

[384]  T. Narancic,et al.  Recent developments in biocatalysis beyond the laboratory , 2015, Biotechnology Letters.

[385]  F. Glorius,et al.  Superparamagnetic nanoparticles for asymmetric catalysis—a perfect match , 2011 .

[386]  Bernhard Hauer,et al.  Catalytic Promiscuity of Halohydrin Dehalogenase and its Application in Enantioselective Epoxide Ring Opening , 2008, Chembiochem : a European journal of chemical biology.

[387]  Lynn F. Gladden,et al.  Glycerol eutectics as sustainable solvent systems , 2010 .

[388]  E. Sousa-Aguiar,et al.  Some important catalytic challenges in the bioethanol integrated biorefinery , 2014 .

[389]  H. Cabana,et al.  Recyclable cross-linked laccase aggregates coupled to magnetic silica microbeads for elimination of pharmaceuticals from municipal wastewater , 2016, Environmental Science and Pollution Research.

[390]  Andrés Illanes,et al.  Production of combi-CLEAs of glycosidases utilized for aroma enhancement in wine , 2015 .

[391]  Oliver May,et al.  Application of designed enzymes in organic synthesis. , 2011, Chemical reviews.

[392]  R. Höfer,et al.  Biomass-based green chemistry: sustainable solutions for modern economies , 2008 .

[393]  Alle Bruggink,et al.  Concepts of Nature in Organic Synthesis: Cascade Catalysis and Multistep Conversions in Concert , 2003 .

[394]  Diego Romano,et al.  An efficient method for the lipase-catalysed resolution and in-line purification of racemic flurbiprofen in a continuous-flow reactor , 2012 .

[395]  David J. C. Constable,et al.  Metrics to ‘green’ chemistry—which are the best? , 2002 .

[396]  U. Schörken,et al.  Native lipase dissolved in hydrophilic green solvents: A versatile 2‐phase reaction system for high yield ester synthesis , 2015 .

[397]  S. Focardi,et al.  Theoretical descriptor for the correlation of aquatic toxicity of ionic liquids by quantitative structure–toxicity relationships , 2011 .

[398]  A. Bhattacharya,et al.  Synergism of fungal and bacterial cellulases and hemicellulases: a novel perspective for enhanced bio-ethanol production , 2015, Biotechnology Letters.

[399]  FDA's policy statement for the development of new stereoisomeric drugs. , 1992, Chirality.

[400]  Jian-He Xu,et al.  New opportunities for biocatalysis: driving the synthesis of chiral chemicals. , 2011, Current opinion in biotechnology.

[401]  Roger A. Sheldon,et al.  Fundamentals of Green Chemistry: Efficiency in Reaction Design , 2012 .