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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Advances in microbial exoenzymes bioengineering for improvement of bioplastics degradation

Chemosphere, Journal Year: 2024, Volume and Issue: 355, P. 141749 - 141749

Published: March 21, 2024

Plastic pollution has become a major global concern, posing numerous challenges for the environment and wildlife. Most conventional ways of plastics degradation are inefficient cause great damage to ecosystems. The development biodegradable offers promising solution waste management. These designed break down under various conditions, opening up new possibilities mitigate negative impact traditional plastics. Microbes, including bacteria fungi, play crucial role in bioplastics by producing secreting extracellular enzymes, such as cutinase, lipases, proteases. However, these microbial enzymes sensitive extreme environmental temperature acidity, affecting their functions stability. To address challenges, scientists have employed protein engineering immobilization techniques enhance enzyme stability predict structures. Strategies improving substrate interaction, increasing thermostability, reinforcing bonding between active site substrate, refining activity being utilized boost functionality. Recently, bioengineering through gene cloning expression potential microorganisms, revolutionized biodegradation bioplastics. This review aimed discuss most recent strategies modifying bioplastic-degrading terms functionality, thermostability enhancement, binding site, with other improvement surface action. Additionally, discovered exoenzymes metagenomics were emphasized.

Language: Английский

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Engineering Enzymes for Environmental Sustainability

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(52)

Published: Aug. 31, 2023

Abstract The development and implementation of sustainable catalytic technologies is key to delivering our net‐zero targets. Here we review how engineered enzymes, with a focus on those developed using directed evolution, can be deployed improve the sustainability numerous processes help conserve environment. Efficient robust biocatalysts have been capture carbon dioxide (CO 2 ) embedded into new efficient metabolic CO fixation pathways. Enzymes refined for bioremediation, enhancing their ability degrade toxic harmful pollutants. Biocatalytic recycling gaining momentum, cutinases PETases depolymerization abundant plastic, polyethylene terephthalate (PET). Finally, biocatalytic approaches accessing petroleum‐based feedstocks chemicals are expanding, optimized enzymes convert plant biomass biofuels or other high value products. Through these examples, hope illustrate enzyme engineering biocatalysis contribute cleaner more chemical industry.

Language: Английский

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Imine Reductases and Reductive Aminases in Organic Synthesis

ACS Catalysis, Journal Year: 2024, Volume and Issue: unknown, P. 14308 - 14329

Published: Sept. 12, 2024

Language: Английский

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Cell-free systems: A synthetic biology tool for rapid prototyping in metabolic engineering

Biotechnology Advances, Journal Year: 2025, Volume and Issue: unknown, P. 108522 - 108522

Published: Jan. 1, 2025

Language: Английский

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Data‐Driven Protein Engineering for Improving Catalytic Activity and Selectivity

ChemBioChem, Journal Year: 2023, Volume and Issue: 25(3)

Published: Nov. 29, 2023

Abstract Protein engineering is essential for altering the substrate scope, catalytic activity and selectivity of enzymes applications in biocatalysis. However, traditional approaches, such as directed evolution rational design, encounter challenge dealing with experimental screening process a large protein mutation space. Machine learning methods allow approximation fitness landscapes identification patterns using limited data, thus providing new avenue to guide campaigns. In this concept article, we review machine models that have been developed assess enzyme‐substrate‐catalysis performance relationships aiming improve through data‐driven engineering. Furthermore, prospect future development field provide additional strategies tools achieving desired activities selectivities.

Language: Английский

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Selection of a promiscuous minimalist cAMP phosphodiesterase from a library of de novo designed proteins

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(7), P. 1200 - 1208

Published: May 3, 2024

Abstract The ability of unevolved amino acid sequences to become biological catalysts was key the emergence life on Earth. However, billions years evolution separate complex modern enzymes from their simpler early ancestors. To probe how can develop new functions, we use ultrahigh-throughput droplet microfluidics screen for phosphoesterase activity amidst a library more than one million based de novo designed 4-helix bundle. Characterization hits revealed that acquisition function involved large jump in sequence space enriching truncations removed >40% protein chain. Biophysical characterization catalytically active truncated it dimerizes into an α-helical structure, with gain accompanied by increased structural dynamics. identified phosphodiesterase is manganese-dependent metalloenzyme hydrolyses range phosphodiesters. It most towards cyclic AMP, rate acceleration ~10 9 and catalytic proficiency >10 14 M −1 , comparable larger shaped evolution.

Language: Английский

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A versatile microbial platform as a tunable whole-cell chemical sensor

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 27, 2024

Language: Английский

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Addressing epistasis in the design of protein function

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(34)

Published: Aug. 12, 2024

Mutations in protein active sites can dramatically improve function. The site, however, is densely packed and extremely sensitive to mutations. Therefore, some mutations may only be tolerated combination with others a phenomenon known as epistasis. Epistasis reduces the likelihood of obtaining improved functional variants slows natural lab evolutionary processes. Research has shed light on molecular origins epistasis its role shaping trajectories outcomes. In addition, sequence- AI-based strategies that infer epistatic relationships from mutational patterns or experimental evolution data have been used design variants. recent years, combinations such approaches atomistic calculations successfully predicted highly combinatorial sites. These were thousands active-site variants, demonstrating that, while our understanding remains incomplete, determinants are critical for accurate now sufficiently understood. We conclude space explored by expanded enhance activities discover new ones. Furthermore, opens way systematically exploring sequence structure impacts function, deepening control over activity.

Language: Английский

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Microdroplet screening rapidly profiles a biocatalyst to enable its AI-assisted engineering

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 8, 2024

Abstract Engineering enzyme biocatalysts for higher efficiency is key to enabling sustainable, ‘green’ production processes the chemical and pharmaceutical industry. This challenge can be tackled from two angles: by directed evolution, based on labor-intensive experimental testing of variant libraries, or computational methods, where sequence-function data are used predict biocatalyst improvements. Here, we combine both approaches into a two-week workflow, ultra-high throughput screening library imine reductases (IREDs) in microfluidic devices provides not only selected ‘hits’, but also long-read sequence linked fitness scores >17 thousand variants. We demonstrate engineering an IRED chiral amine synthesis mapping functional information one go, ready interpretation extrapolation protein engineers with help machine learning (ML). calculate position-dependent mutability combinability mutations comprehensively illuminate complex interplay driven synergistic, often positively epistatic effects. Interpreted easy-to-use regression tree-based ML algorithms designed suit evaluation random whole-gene mutagenesis data, 3-fold improved ‘hits’ obtained extrapolated further give up 23-fold improvements catalytic rate after handful mutants. Our campaign paradigmatic future that will rely access large maps as profiles way responds mutation. These chart function exploiting synergy rapid combined extrapolation.

Language: Английский

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