Immobilization of lipases on hydrophobic supports: immobilization mechanism, advantages, problems, and solutions

Biotechnology Advances, Journal Year: 2019, Volume and Issue: 37(5), P. 746 - 770

Published: April 8, 2019

Language: Английский

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Machine learning-assisted directed protein evolution with combinatorial libraries

Proceedings of the National Academy of Sciences, Journal Year: 2019, Volume and Issue: 116(18), P. 8852 - 8858

Published: April 12, 2019

To reduce experimental effort associated with directed protein evolution and to explore the sequence space encoded by mutating multiple positions simultaneously, we incorporate machine learning in workflow. Combinatorial can be quite expensive sample experimentally, but models trained on tested variants provide a fast method for testing computationally. We validate this approach large published empirical fitness landscape human GB1 binding protein, demonstrating that learning-guided finds higher than those found other approaches. then an example application evolving enzyme produce each of two possible product enantiomers (stereodivergence) new-to-nature carbene Si-H insertion reaction. The predicted libraries enriched functional enzymes fixed seven mutations rounds identify selective catalysis 93% 79% ee. By greatly increasing throughput silico modeling, enhances quality diversity solutions engineering problem.

Language: Английский

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Directed Evolution: Methodologies and Applications

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(20), P. 12384 - 12444

Published: July 23, 2021

Directed evolution aims to expedite the natural process of biological molecules and systems in a test tube through iterative rounds gene diversifications library screening/selection. It has become one most powerful widespread tools for engineering improved or novel functions proteins, metabolic pathways, even whole genomes. This review describes commonly used diversification strategies, screening/selection methods, recently developed continuous strategies directed evolution. Moreover, we highlight some representative applications nucleic acids, genetic circuits, viruses, cells. Finally, discuss challenges future perspectives

Language: Английский

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Innovation by Evolution: Bringing New Chemistry to Life (Nobel Lecture)

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 58(41), P. 14420 - 14426

Published: Aug. 21, 2019

The directed evolution of enzymes is now routinely used to develop new catalysts with various applications, such as in environmentally friendly production chemicals and renewable fuels. In her Nobel lecture, F. Arnold describes how lessons from nature inspired the development methods for evolution.

Language: Английский

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Synthetic biology strategies for microbial biosynthesis of plant natural products

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: May 13, 2019

Abstract Metabolic engineers endeavor to create a bio-based manufacturing industry using microbes produce fuels, chemicals, and medicines. Plant natural products (PNPs) are historically challenging ubiquitous in medicines, flavors, fragrances. Engineering PNP pathways into new hosts requires finding or modifying suitable host accommodate the pathway, planning implementing biosynthetic route compound, discovering engineering enzymes for missing steps. In this review, we describe recent developments metabolic at level of host, enzyme, discuss how field is approaching ever more complex opportunities.

Language: Английский

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Broadening the Scope of Biocatalysis in Sustainable Organic Synthesis

ChemSusChem, Journal Year: 2019, Volume and Issue: 12(13), P. 2859 - 2881

Published: April 1, 2019

Abstract This Review is aimed at synthetic organic chemists who may be familiar with organometallic catalysis but have no experience biocatalysis, and seeks to provide an answer the perennial question: if it so attractive, why wasn't extensively used in past? The development of biocatalysis industrial synthesis traced from middle last century. Advances molecular biology two decades, particular genome sequencing, gene directed evolution proteins, enabled remarkable improvements scope substantially reduced biocatalyst times cost contributions. Additionally, recovery reuse been facilitated by developments enzyme immobilization technologies. Biocatalysis has become eminently competitive chemocatalysis biocatalytic production important pharmaceutical intermediates, such as enantiopure alcohols amines, mainstream synthesis. space significantly expanded currently being extended even further include new‐to‐nature reactions.

Language: Английский

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The importance of catalytic promiscuity for enzyme design and evolution

Nature Reviews Chemistry, Journal Year: 2019, Volume and Issue: 3(12), P. 687 - 705

Published: Nov. 15, 2019

Language: Английский

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The Hitchhiker's guide to biocatalysis: recent advances in the use of enzymes in organic synthesis

Chemical Science, Journal Year: 2020, Volume and Issue: 11(10), P. 2587 - 2605

Published: Jan. 1, 2020

Enzymes are excellent catalysts that increasingly being used in industry and academia. This Perspective provides a general practical guide to enzymes their synthetic potential, primarily aimed at organic chemists.

Language: Английский

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Directed evolution of an efficient and thermostable PET depolymerase

Nature Catalysis, Journal Year: 2022, Volume and Issue: 5(8), P. 673 - 681

Published: Aug. 11, 2022

Language: Английский

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Peptide-Based Catalysts Reach the Outer Sphere through Remote Desymmetrization and Atroposelectivity

Accounts of Chemical Research, Journal Year: 2018, Volume and Issue: 52(1), P. 199 - 215

Published: Dec. 11, 2018

ConspectusNature's catalytic machinery has provided endless inspiration for chemists. While the enzymatic ideal yet to be fully realized, field made tremendous strides toward synthetic, small-molecule catalysts a wide array of transformations, often drawing upon biological concepts in their design. One strategy that been particularly influenced by enzymology is peptide catalysis, wherein oligopeptides are implemented as chiral synthetically relevant reactions. The fundamental goal mimic active sites taking advantage secondary structures allow multifunctional activation substrates within framework significantly reduced molecular complexity.Our group now studying peptide-based catalysis over two decades. At outset, there were many reasons concerned general contributions might not possible. Precedents existed, including Juliá–Colonna epoxidations mediated helical oligopeptides, among others. However, we sought explore whether could find broad applications organic synthesis despite what was expected principal liability: conformational flexibility. Over time, have able identify peptidic variety site- and enantioselective transformations ranging from hydroxyl arene functionalizations redox C–C bond forming peptides exhibited excellent activities, cases enabling never-before-seen patterns selectivity. Recent studies even suggest that, certain situations, flexibility these may advantageous asymmetric induction.In course our studies, opportunities employ solve long-standing stereochemically intriguing problems presented themselves. For example, found provide exceptional enantiotopic differentiation desymmetrization Early results with symmetrical polyol substrates, such myo-inositols glycerols, eventually spurred development remote desymmetrizations diarylmethanes, which groups separated prochiral center ∼6 Å one another nearly 1 nm. Various electrophilic brominations, well C–C, C–O, C–N cross-coupling reactions using ligands on copper(I) developed this reaction archetype. Additionally, preponderance axially chiral, atropisomeric compounds ligands, organocatalysts, pharmacophores encouraged us atroposelective catalysts. We peptide-catalyzed brominations pharmaceutically biaryl, non-biaryl, hetero-biaryl atropisomers take dynamic kinetic resolution schemes. These projects vastly expanded reach original hypotheses raised new questions about extent they enzymes.Herein, recount optimization complex reactions, particular focus structural mechanistic aspects make them well-suited respective functions. ability address important fundamentally challenging issues combined modularity ease-of-synthesis, primed future use synthesis.

Language: Английский

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