New advances in protein engineering for industrial applications: Key takeaways DOI Creative Commons

Giles Obinna Ndochinwa,

Qingyan Wang,

Nkwachukwu Oziamara Okoro

et al.

Open Life Sciences, Journal Year: 2024, Volume and Issue: 19(1)

Published: Jan. 1, 2024

Abstract Recent advancements in protein/enzyme engineering have enabled the production of a diverse array high-value compounds microbial systems with potential for industrial applications. The goal this review is to articulate some most recent protein advances bacteria, yeast, and other produce valuable substances. These substances include α-farnesene, vitamin B12, fumaric acid, linalool, glucaric carminic mycosporine-like amino acids, patchoulol, orcinol glucoside, d -lactic keratinase, α-glucanotransferases, β-glucosidase, seleno-methylselenocysteine, fatty high-efficiency β-glucosidase enzymes, cellulase, β-carotene, physcion, glucoamylase. Additionally, enzyme enhancing thermostability will be discussed. findings revolutionize various industries, including biotechnology, food, pharmaceuticals, biofuels.

Language: Английский

From nature to industry: Harnessing enzymes for biocatalysis DOI
Rebecca Buller, Stefan Lutz, Romas J. Kazlauskas

et al.

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

Citations

224
Stereoselective amino acid synthesis by photobiocatalytic oxidative coupling DOI

Tian-Ci Wang,

Binh Khanh, Zheng Zhang

et al.

Nature, Journal Year: 2024, Volume and Issue: 629(8010), P. 98 - 104

Published: May 1, 2024

Language: Английский

Citations

34
Expanding chemistry through in vitro and in vivo biocatalysis DOI
Elijah N. Kissman, Max B. Sosa,

Douglas C Millar

et al.

Nature, Journal Year: 2024, Volume and Issue: 631(8019), P. 37 - 48

Published: July 3, 2024

Language: Английский

Citations

31
The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins DOI
Vinayak Agarwal, Andrew C. McShan

Nature Chemical Biology, Journal Year: 2024, Volume and Issue: 20(8), P. 950 - 959

Published: June 21, 2024

Language: Английский

Citations

30
From Ground-State to Excited-State Activation Modes: Flavin-Dependent “Ene”-Reductases Catalyzed Non-natural Radical Reactions DOI
Haigen Fu, Todd K. Hyster

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(9), P. 1446 - 1457

Published: April 11, 2024

ConspectusEnzymes are desired catalysts for chemical synthesis, because they can be engineered to provide unparalleled levels of efficiency and selectivity. Yet, despite the astonishing array reactions catalyzed by natural enzymes, many reactivity patterns found in small molecule have no counterpart living world. With a detailed understanding mechanisms utilized catalysts, we identify existing enzymes with potential catalyze that currently unknown nature. Over past eight years, our group has demonstrated flavin-dependent "ene"-reductases (EREDs) various radical-mediated selectivity, solving long-standing challenges asymmetric synthesis.This Account presents development EREDs as general radical reactions. While developed multiple generating radicals within protein active sites, this account will focus on examples where flavin mononucleotide hydroquinone (FMNhq) serves an electron transfer initiator. initial mechanistic hypotheses were rooted electron-transfer-based initiation commonly used synthetic organic chemists, ultimately uncovered emergent unique site. We begin covering intramolecular discussing how activates substrate reduction altering redox-potential alkyl halides templating charge complex between flavin-cofactor. Protein engineering been modify fundamental photophysics these reactions, highlighting opportunity tune systems further using directed evolution. This section highlights range coupling partners termination available reactions.The next intermolecular role enzyme-templated ternary complexes among cofactor, halide, partner gating ensure it only occurs when both substrates bound highlight applications activation mode, including olefin hydroalkylation, carbohydroxylation, arene functionalization, nitronate alkylation. also discusses favor steps elusive solution reductive nitroalkanes. aware several recent EREDs-catalyzed photoenzymatic transformations from other groups. discuss results papers context nuances substrates.These biocatalytic often complement state-of-the-art small-molecule-catalyzed making valuable addition chemist's toolbox. Moreover, underlying principles studied potentially operative cofactor-dependent proteins, opening door different types enzyme-catalyzed anticipate serve guide inspire broad interest repurposing access new transformations.

Language: Английский

Citations

24
Synergistic Photoenzymatic Catalysis Enables Synthesis of a-Tertiary Amino Acids Using Threonine Aldolases DOI

Yao Ouyang,

Claire G. Page,

Catherine Bilodeau

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(20), P. 13754 - 13759

Published: May 13, 2024

a-Tertiary amino acids are essential components of drugs and agrochemicals, yet traditional syntheses step-intensive provide access to a limited range structures with varying levels enantioselectivity. Here, we report the α-alkylation unprotected alanine glycine by pyridinium salts using pyridoxal (PLP)-dependent threonine aldolases Rose Bengal photoredox catalyst. The strategy efficiently prepares various a-tertiary in single chemical step as enantiomer. UV–vis spectroscopy studies reveal ternary interaction between salt, protein, photocatalyst, which hypothesize is responsible for localizing radical formation active site. This method highlights opportunity combining catalysts enzymes new catalytic functions known enzymes.

Language: Английский

Citations

23
Machine learning-guided co-optimization of fitness and diversity facilitates combinatorial library design in enzyme engineering DOI Creative Commons
Kerr Ding, M. A. Chin, Yunlong Zhao

et al.

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

Published: July 29, 2024

Abstract The effective design of combinatorial libraries to balance fitness and diversity facilitates the engineering useful enzyme functions, particularly those that are poorly characterized or unknown in biology. We introduce MODIFY, a machine learning (ML) algorithm learns from natural protein sequences infer evolutionarily plausible mutations predict fitness. MODIFY co-optimizes predicted sequence starting libraries, prioritizing high-fitness variants while ensuring broad coverage. In silico evaluation shows outperforms state-of-the-art unsupervised methods zero-shot prediction enables ML-guided directed evolution with enhanced efficiency. Using we engineer generalist biocatalysts derived thermostable cytochrome c achieve enantioselective C-B C-Si bond formation via new-to-nature carbene transfer mechanism, leading six away previously developed enzymes exhibiting superior comparable activities. These results demonstrate MODIFY’s potential solving challenging problems beyond reach classic evolution.

Language: Английский

Citations

22
Stereodivergent photobiocatalytic radical cyclization through the repurposing and directed evolution of fatty acid photodecarboxylases DOI
Shuyun Ju, Dian Li, Binh Khanh

et al.

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(8), P. 1339 - 1347

Published: April 17, 2024

Language: Английский

Citations

20
Biocatalytic enantioselective C(sp3)–H fluorination enabled by directed evolution of non-haem iron enzymes DOI
Liupeng Zhao, Binh Khanh, Lida Cheng

et al.

Nature Synthesis, Journal Year: 2024, Volume and Issue: 3(8), P. 967 - 975

Published: April 26, 2024

Language: Английский

Citations

18
Asymmetric photoenzymatic incorporation of fluorinated motifs into olefins DOI
Mao‐Lin Li, Yaru Yuan, Wesley Harrison

et al.

Science, Journal Year: 2024, Volume and Issue: 385(6707), P. 416 - 421

Published: July 25, 2024

Enzymes capable of assimilating fluorinated feedstocks are scarce. This situation poses a challenge for the biosynthesis compounds used in pharmaceuticals, agrochemicals, and materials. We developed photoenzymatic hydrofluoroalkylation that integrates motifs into olefins. The photoinduced promiscuity flavin-dependent ene-reductases enables generation carbon-centered radicals from iodinated fluoroalkanes, which directed by photoenzyme to engage enantioselectively with approach facilitates stereocontrol through interaction between singular unit enzyme, securing high enantioselectivity at β, γ, or δ positions groups enzymatic hydrogen atom transfer-a process is notably challenging conventional chemocatalysis. work advances strategies integrating chemical opens avenues asymmetric synthesis compounds.

Language: Английский

Citations

17