Industrially Relevant Enzyme Cascades for Drug Synthesis and Their Ecological Assessment DOI Open Access
Regine Siedentop, Katrin Rosenthal

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3605 - 3605

Published: March 25, 2022

Environmentally friendly and sustainable processes for the production of active pharmaceutical ingredients (APIs) gain increasing attention. Biocatalytic synthesis routes with enzyme cascades support many stated green principles, example, reduced need solvents or biodegradability enzymes. Multi-enzyme reactions have even more advantages such as shift equilibrium towards product side, no intermediate isolation, complex molecules in one reaction pot. Despite intriguing benefits, only a few been applied industry so far. However, several new are currently being developed research that could be great importance to industry. Here, we present multi-enzymatic API close an industrial application. Their performances comparable exceed their chemical counterparts. A still development also introduced this review. Economic ecological considerations made some example assess environmental friendliness applicability.

Language: Английский

Is enzyme immobilization a mature discipline? Some critical considerations to capitalize on the benefits of immobilization DOI Creative Commons
Juan M. Bolívar, John M. Woodley, Roberto Fernandéz‐Lafuente

et al.

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(15), P. 6251 - 6290

Published: Jan. 1, 2022

Enzyme immobilization has been developing since the 1960s and although many industrial biocatalytic processes use technology to improve enzyme performance, still today we are far from full exploitation of field. One clear reason is that evaluate based on only a few experiments not always well-designed. In contrast other reviews subject, here highlight pitfalls using incorrectly designed protocols explain why in cases sub-optimal results obtained. We also describe solutions overcome these challenges come conclusion recent developments material science, bioprocess engineering protein science continue open new opportunities for future. this way, immobilization, being mature discipline, remains as subject high interest where intense research necessary take advantage possibilities.

Language: Английский

Citations

355

Green Chemistry, Biocatalysis, and the Chemical Industry of the Future DOI
Roger A. Sheldon, Dean Brady

ChemSusChem, Journal Year: 2022, Volume and Issue: 15(9)

Published: Jan. 13, 2022

In the movement to decarbonize our economy and move away from fossil fuels we will need harness waste products of activities, such as lignocellulose, methane, carbon dioxide. Our wastes be integrated into a circular where used are recycled manufacturing cycle. Key this recycling plastics at resin monomer levels. Biotechnology is well suited future chemical industry that must adapt widely distributed diverse biological feedstocks. increasing mastery biotechnology allowing us develop enzymes organisms can synthesize widening selection desirable bulk chemicals, including plastics, commercially viable productivities. Integration bioreactors with electrochemical systems permit new production opportunities enhanced productivities advantage using low-carbon electricity renewable sustainable sources.

Language: Английский

Citations

128

Enzyme Immobilization and Co-Immobilization: Main Framework, Advances and Some Applications DOI Open Access

Joaquim Bié,

Bruno Sepodes, Pedro Fernandes

et al.

Processes, Journal Year: 2022, Volume and Issue: 10(3), P. 494 - 494

Published: March 1, 2022

Enzymes are outstanding (bio)catalysts, not solely on account of their ability to increase reaction rates by up several orders magnitude but also for the high degree substrate specificity, regiospecificity and stereospecificity. The use development enzymes as robust biocatalysts is one main challenges in biotechnology. However, despite specificities turnover enzymes, there drawbacks. At industrial level, these drawbacks typically overcome resorting immobilized enhance stability. Immobilization allows reuse, increases stability, facilitates process control, eases product recovery, enhances yield quality. This especially important expensive those obtained low fermentation with relatively activity. review provides an integrated perspective (multi)enzyme immobilization that abridges a critical evaluation methods carriers, biocatalyst metrics, impact key carrier features performance, trends towards miniaturization detailed illustrative examples representative biocatalytic applications promoting sustainability.

Language: Английский

Citations

103

Biocatalysis as Key to Sustainable Industrial Chemistry DOI
Andrés R. Alcántara, Pablo Domı́nguez de Marı́a, Jennifer A. Littlechild

et al.

ChemSusChem, Journal Year: 2022, Volume and Issue: 15(9)

Published: March 3, 2022

The role and power of biocatalysis in sustainable chemistry has been continuously brought forward step by to its present outstanding position. problem-solving capabilities have realized numerous substantial achievements biology, engineering. Advances breakthroughs the life sciences interdisciplinary cooperation with clearly accelerated implementation biocatalytic synthesis modern chemistry. Resource-efficient manufacturing processes already provided benefits as well customer-centric value creation pharmaceutical, food, flavor, fragrance, vitamin, agrochemical, polymer, specialty, fine chemical industries. Biocatalysis can make significant contributions not only processes, but also design completely new value-creation chains. now be considered a key enabling technology implement

Language: Английский

Citations

102

Expanding the Synthetic Toolbox through Metal–Enzyme Cascade Reactions DOI
Sergio González‐Granda, Jesús Albarrán‐Velo, Iván Lavandera

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(9), P. 5297 - 5346

Published: Jan. 10, 2023

The combination of metal-, photo-, enzyme-, and/or organocatalysis provides multiple synthetic solutions, especially when the creation chiral centers is involved. Historically, enzymes and transition metal species have been exploited simultaneously through dynamic kinetic resolutions racemates. However, more recently, linear cascades appeared as elegant solutions for preparation valuable organic molecules combining bioprocesses metal-catalyzed transformations. Many advantages are derived from this symbiosis, although there still bottlenecks to be addressed including successful coexistence both catalyst types, need compatible reaction media mild conditions, or minimization cross-reactivities. Therefore, here also provided by means coimmobilization, compartmentalization strategies, flow chemistry, etc. A comprehensive review presented focusing on period 2015 early 2022, which has divided into two main sections that comprise first use metals independent catalysts but working in an orchestral sequential manner, later their application bionanohybrid materials coimmobilization adequate supports. Each part classified different subheadings, based catalyzed catalyst, while development nonasymmetric stereoselective processes was considered section.

Language: Английский

Citations

60

Enantioselective Transformations in the Synthesis of Therapeutic Agents DOI
Yang He,

Hanxiao Yu,

I. Stolarzewicz

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(15), P. 9397 - 9446

Published: July 7, 2023

The proportion of approved chiral drugs and drug candidates under medical studies has surged dramatically over the past two decades. As a consequence, efficient synthesis enantiopure pharmaceuticals or their synthetic intermediates poses profound challenge to medicinal process chemists. significant advancement in asymmetric catalysis provided an effective reliable solution this challenge. successful application transition metal catalysis, organocatalysis, biocatalysis pharmaceutical industries promoted discovery by precise preparation enantio-enriched therapeutic agents, facilitated industrial production active ingredient economic environmentally friendly fashion. present review summarizes most recent applications (2008–2022) industry ranging from scales pilot levels. It also showcases latest achievements trends agents with state art technologies catalysis.

Language: Английский

Citations

43

Navigating the landscape of enzyme design: from molecular simulations to machine learning DOI Creative Commons
Jiahui Zhou, Meilan Huang

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(16), P. 8202 - 8239

Published: Jan. 1, 2024

Global environmental issues and sustainable development call for new technologies fine chemical synthesis waste valorization. Biocatalysis has attracted great attention as the alternative to traditional organic synthesis. However, it is challenging navigate vast sequence space identify those proteins with admirable biocatalytic functions. The recent of deep-learning based structure prediction methods such AlphaFold2 reinforced by different computational simulations or multiscale calculations largely expanded 3D databases enabled structure-based design. While approaches shed light on site-specific enzyme engineering, they are not suitable large-scale screening potential biocatalysts. Effective utilization big data using machine learning techniques opens up a era accelerated predictions. Here, we review applications machine-learning guided We also provide our view challenges perspectives effectively employing design integrating molecular learning, importance database construction algorithm in attaining predictive ML models explore fitness landscape

Language: Английский

Citations

21

The Time and Place for Nature in Drug Discovery DOI Creative Commons
Robert J. Young, Sabine L. Flitsch, Michael Grigalunas

et al.

JACS Au, Journal Year: 2022, Volume and Issue: 2(11), P. 2400 - 2416

Published: Oct. 14, 2022

The case for a renewed focus on Nature in drug discovery is reviewed; not terms of natural product screening, but how and why biomimetic molecules, especially those produced by processes, should deliver the age artificial intelligence screening vast collections both vitro silico. declining product-likeness licensed drugs consequent physicochemical implications this trend context current practices are noted. To arrest these trends, logic seeking new bioactive agents with enhanced mimicry considered; notably that molecules constructed proteins (enzymes) more likely to interact other (e.g., targets transporters), notion validated products. Nature's finite number building blocks their interactions necessarily reduce potential numbers structures, yet enable expansion chemical space inherent diversity physical characteristics, pertinent property-based design. feasible variations motifs considered expanded encompass pseudo-natural products, leading further logical step harnessing bioprocessing routes access them. Together, offer opportunities enhancing mimicry, thereby bringing innovation synthesis exploiting characteristics recognition processes. computational guidance help identifying binding commonalities route map opportunity design tailored "organic/biological" rather than purely "synthetic" structures. prototype structures pay dividends disposition efficacy while inherently enabling greener sustainable manufacturing techniques.

Language: Английский

Citations

67

Putting precision and elegance in enzyme immobilisation with bio-orthogonal chemistry DOI Creative Commons
Xiaolin Pei, Zhiyuan Luo, Li Qiao

et al.

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 51(16), P. 7281 - 7304

Published: Jan. 1, 2022

The covalent immobilisation of enzymes generally involves the use highly reactive crosslinkers, such as glutaraldehyde, to couple enzyme molecules each other or carriers through, for example, free amino groups lysine residues, on surface. Unfortunately, methods suffer from a lack precision. Random formation linkages with functional in leads disruption three dimensional structure and accompanying activity losses. This review focuses recent advances bio-orthogonal chemistry conjunction rec-DNA affect precise enzymes. In this way, cost-effective combination production, purification an is achieved, single unit operation high degree Various techniques putting precision elegance into are elaborated. These include, fusing (grafting) peptide protein tags target that enable its cell lysate incorporating non-standard acids application chemistry.

Language: Английский

Citations

53

A review on the immobilization of pepsin: A Lys-poor enzyme that is unstable at alkaline pH values DOI Creative Commons
Roberto Morellon‐Sterling, Olga Luisa Tavano, Juan M. Bolívar

et al.

International Journal of Biological Macromolecules, Journal Year: 2022, Volume and Issue: 210, P. 682 - 702

Published: May 1, 2022

Pepsin is a protease used in many different applications, and instances, it utilized an immobilized form to prevent contamination of the reaction product. This enzyme has two peculiarities that make its immobilization complex. The first one related poor presence primary amino groups on surface (just Lys terminal group). second stability at alkaline pH values. Both features this be considered complicated goal, as most protocols utilize for immobilization. review presents some attempts get pepsin biocatalyst their applications. high density anionic (Asp Glu) anion exchange simpler, but makes strategies immobilize (e.g., amino-glutaraldehyde supports) more mixed ion exchange/hydrophobic adsorption than real covalent Finally, we propose possibilities can permit not only enzyme, also stabilization via multipoint attachment.

Language: Английский

Citations

49