From nature to industry: Harnessing enzymes for biocatalysis

Science, Год журнала: 2023, Номер 382(6673)

Опубликована: Ноя. 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.

Язык: Английский

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Stereoselective amino acid synthesis by photobiocatalytic oxidative coupling

Nature, Год журнала: 2024, Номер 629(8010), С. 98 - 104

Опубликована: Май 1, 2024

Язык: Английский

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Expanding chemistry through in vitro and in vivo biocatalysis

Nature, Год журнала: 2024, Номер 631(8019), С. 37 - 48

Опубликована: Июль 3, 2024

Язык: Английский

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The power and pitfalls of AlphaFold2 for structure prediction beyond rigid globular proteins

Nature Chemical Biology, Год журнала: 2024, Номер 20(8), С. 950 - 959

Опубликована: Июнь 21, 2024

Язык: Английский

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From Ground-State to Excited-State Activation Modes: Flavin-Dependent “Ene”-Reductases Catalyzed Non-natural Radical Reactions

Accounts of Chemical Research, Год журнала: 2024, Номер 57(9), С. 1446 - 1457

Опубликована: Апрель 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.

Язык: Английский

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

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(20), С. 13754 - 13759

Опубликована: Май 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.

Язык: Английский

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Machine learning-guided co-optimization of fitness and diversity facilitates combinatorial library design in enzyme engineering

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 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.

Язык: Английский

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Stereodivergent photobiocatalytic radical cyclization through the repurposing and directed evolution of fatty acid photodecarboxylases

Nature Chemistry, Год журнала: 2024, Номер 16(8), С. 1339 - 1347

Опубликована: Апрель 17, 2024

Язык: Английский

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Biocatalytic enantioselective C(sp3)–H fluorination enabled by directed evolution of non-haem iron enzymes

Nature Synthesis, Год журнала: 2024, Номер 3(8), С. 967 - 975

Опубликована: Апрель 26, 2024

Язык: Английский

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Asymmetric photoenzymatic incorporation of fluorinated motifs into olefins

Science, Год журнала: 2024, Номер 385(6707), С. 416 - 421

Опубликована: Июль 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.

Язык: Английский

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