From nature to industry: Harnessing enzymes for biocatalysis

Science, Journal Year: 2023, Volume and Issue: 382(6673)

Published: Nov. 23, 2023

Biocatalysis harnesses enzymes to make valuable products. This green technology is used in countless applications from bench scale industrial production and allows practitioners access complex organic molecules, often with fewer synthetic steps reduced waste. The last decade has seen an explosion the development of experimental computational tools tailor enzymatic properties, equipping enzyme engineers ability create biocatalysts that perform reactions not present nature. By using (chemo)-enzymatic synthesis routes or orchestrating intricate cascades, scientists can synthesize elaborate targets ranging DNA pharmaceuticals starch made vitro CO2-derived methanol. In addition, new chemistries have emerged through combination biocatalysis transition metal catalysis, photocatalysis, electrocatalysis. review highlights recent key developments, identifies current limitations, provides a future prospect for this rapidly developing technology.

Language: Английский

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Enantioselective [2+2]-cycloadditions with triplet photoenzymes

Nature, Journal Year: 2022, Volume and Issue: 611(7937), P. 715 - 720

Published: Sept. 21, 2022

Language: Английский

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A designed photoenzyme for enantioselective [2+2] cycloadditions

Nature, Journal Year: 2022, Volume and Issue: 611(7937), P. 709 - 714

Published: Sept. 21, 2022

Language: Английский

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Plastic Waste Valorization by Leveraging Multidisciplinary Catalytic Technologies

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(15), P. 9307 - 9324

Published: July 18, 2022

Plastic waste triggers a series of concerns because its disruptive impact on the environment and ecosystem. From point view catalysis, however, end-of-life plastics can be seen as an untapped feedstock for preparation value-added products. Thus, development diversified catalytic approaches valorization is urgent. Previous reviews this field have systematically summarized progress made plastic reclamation. In review, we emphasize design processes by leveraging state-of-the-art technologies from other developed fields to derive valuable polymers, functional materials, chemicals plastics. The principles, mechanisms, opportunities chemical (thermo-, electro-, photocatalytic) well biocatalytic ones are discussed, which may provide more insights future processes. Finally, outlooks perspectives accelerate toward feasible economy discussed.

Language: Английский

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De novo protein design—From new structures to programmable functions

Cell, Journal Year: 2024, Volume and Issue: 187(3), P. 526 - 544

Published: Feb. 1, 2024

Methods from artificial intelligence (AI) trained on large datasets of sequences and structures can now "write" proteins with new shapes molecular functions de novo, without starting found in nature. In this Perspective, I will discuss the state field novo protein design at juncture physics-based modeling approaches AI. New folds higher-order assemblies be designed considerable experimental success rates, difficult problems requiring tunable control over conformations precise shape complementarity for recognition are coming into reach. Emerging incorporate engineering principles-tunability, controllability, modularity-into process beginning. Exciting frontiers lie deconstructing cellular and, conversely, constructing synthetic signaling ground up. As methods improve, many more challenges unsolved.

Language: Английский

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The Evolving Nature of Biocatalysis in Pharmaceutical Research and Development

JACS Au, Journal Year: 2023, Volume and Issue: 3(3), P. 715 - 735

Published: Feb. 27, 2023

Biocatalysis is a highly valued enabling technology for pharmaceutical research and development as it can unlock synthetic routes to complex chiral motifs with unparalleled selectivity efficiency. This perspective aims review recent advances in the implementation of biocatalysis across early late-stage focus on processes preparative-scale syntheses.

Language: Английский

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Engineered enzymes for the synthesis of pharmaceuticals and other high-value products

Nature Synthesis, Journal Year: 2024, Volume and Issue: 3(1), P. 19 - 32

Published: Jan. 4, 2024

Language: Английский

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Protein generation with evolutionary diffusion: sequence is all you need

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 12, 2023

Abstract Deep generative models are increasingly powerful tools for the in silico design of novel proteins. Recently, a family called diffusion has demonstrated ability to generate biologically plausible proteins that dissimilar any actual seen nature, enabling unprecedented capability and control de novo protein design. However, current state-of-the-art structures, which limits scope their training data restricts generations small biased subset space. Here, we introduce general-purpose framework, EvoDiff, combines evolutionary-scale with distinct conditioning capabilities controllable generation sequence EvoDiff generates high-fidelity, diverse, structurally-plausible cover natural functional We show experimentally express, fold, exhibit expected secondary structure elements. Critically, can inaccessible structure-based models, such as those disordered regions, while maintaining scaffolds structural motifs. validate universality our sequence-based formulation by characterizing intrinsically-disordered mitochondrial targeting signals, metal-binding proteins, binders designed using EvoDiff. envision will expand engineering beyond structure-function paradigm toward programmable, sequence-first

Language: Английский

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Combinatorial assembly and design of enzymes

Science, Journal Year: 2023, Volume and Issue: 379(6628), P. 195 - 201

Published: Jan. 12, 2023

The design of structurally diverse enzymes is constrained by long-range interactions that are necessary for accurate folding. We introduce an atomistic and machine learning strategy the combinatorial assembly (CADENZ) to fragments combine with one another generate diverse, low-energy structures stable catalytic constellations. applied CADENZ endoxylanases used activity-based protein profiling recover thousands enzymes. Functional designs exhibit high active-site preorganization more compact packing outside active site. Implementing these lessons into led a 10-fold improved hit rate than 10,000 recovered This design-test-learn loop can be applied, in principle, any modular family, yielding huge diversity general on principles.

Language: Английский

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The Quantum Chemical Cluster Approach in Biocatalysis

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(8), P. 938 - 947

Published: March 28, 2023

The quantum chemical cluster approach has been used for modeling enzyme active sites and reaction mechanisms more than two decades. In this methodology, a relatively small part of the around site is selected as model, methods, typically density functional theory, are to calculate energies other properties. surrounding modeled using implicit solvation atom fixing techniques. Over years, large number have solved method. models gradually become larger result faster computers, new kinds questions addressed. Account, we review how can be utilized in field biocatalysis. Examples from our recent work chosen illustrate various aspects methodology. use model explore substrate binding discussed first. It emphasized that comprehensive search necessary order identify lowest-energy mode(s). also argued best mode might not productive one, full reactions enzyme-substrate complexes therefore considered find pathway. Next, examples given help elucidation detailed biocatalytically interesting enzymes, knowledge exploited develop enzymes with functions or understand reasons lack activity toward non-natural substrates. context phenolic acid decarboxylase metal-dependent decarboxylases amidohydrolase superfamily. application investigation enzymatic enantioselectivity discussed. strictosidine synthase case study, where calculations could reproduce rationalize selectivities both natural Finally, discuss guide rational design variants improved selectivity. Acyl transferase Mycobacterium smegmatis serves an instructive example here, which pinpoint factors controlling specificity enantioselectivity. cases Account highlight thus value tool complements experiments computational techniques provides insights existing tailored

Language: Английский

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