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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Expanding chemistry through in vitro and in vivo biocatalysis

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

Published: July 3, 2024

Language: Английский

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Discovery of the Azaserine Biosynthetic Pathway Uncovers a Biological Route for α‐Diazoester Production

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(28)

Published: May 8, 2023

Azaserine is a bacterial metabolite containing biologically unusual and synthetically enabling α-diazoester functional group. Herein, we report the discovery of azaserine (aza) biosynthetic gene cluster from Glycomyces harbinensis. Discovery related clusters reveals previously unappreciated producers, heterologous expression aza confirms its role in assembly. Notably, this encodes homologues hydrazonoacetic acid (HYAA)-producing enzymes, implicating HYAA biosynthesis. Isotope feeding biochemical experiments support hypothesis. These discoveries indicate that 2-electron oxidation hydrazonoacetyl intermediate required for formation, constituting distinct logic diazo Uncovering biological route synthesis now enables production highly versatile carbene precursor cells, facilitating approaches engineering complete carbene-mediated transformations vivo.

Language: Английский

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Diastereo- and Enantioselective Chemoenzymatic Synthesis of Chiral Tricyclic Intermediate of Anti-HIV Drug Lenacapavir

ACS Catalysis, Journal Year: 2025, Volume and Issue: 15(3), P. 2045 - 2052

Published: Jan. 21, 2025

Despite its great potential, the development and implementation of scalable new-to-nature biocatalytic transformations in chemoenzymatic synthesis clinically significant pharmaceuticals still present a considerable challenge. We developed very recently anti-HIV drug lenacapavir's 5/5/3 fused tricyclic fragment featuring an unusual chiral cyclopropane moiety. Key to this is biocatalyst-controlled, fully diastereo- enantiodivergent cyclopropanation highly functionalized vinylpyrazole substrate, granting access all four possible stereoisomers lenacapavir cyclopropane. High-throughput experimentation led discovery heme-dependent globins, including nitrous oxide dioxygenase (NOD) protoglobin (Pgb), as promising biocatalysts. Directed evolution furnished enantioselective (up 99:1 d.r. e.r.). Further downstream chemical cyclization afforded desired tricycle with stereochemical purity.

Language: Английский

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Triumphs and Challenges of Natural Product Discovery in the Postgenomic Era

Annual Review of Biochemistry, Journal Year: 2024, Volume and Issue: 93(1), P. 411 - 445

Published: Aug. 2, 2024

Natural products have played significant roles as medicine and food throughout human history. Here, we first provide a brief historical overview of natural products, their classification biosynthetic origins, the microbiological genetic methods used for discovery. We also describe discuss technologies that revolutionized field, which transitioned from classic genetics to genome-centric discovery approximately two decades ago. then highlight most recent advancements approaches in current postgenomic era, genome mining is standard operation high-throughput analytical allow parallel genes molecules at an unprecedented pace. Finally, new challenges faced by field future systematic heterologous expression strain-independent discovery, promises deliver more vials than ever before.

Language: Английский

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De novo engineering of programmable and multi-functional biomolecular condensates for controlled biosynthesis

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

Published: Sept. 12, 2024

There is a growing interest in the creation of engineered condensates formed via liquid-liquid phase separation (LLPS) to exert precise cellular control prokaryotes. However, de novo design metabolic flux or protein translation remains challenge. Here, we present synthetic condensate platform, generated through incorporation artificial, disordered proteins realize specific functions Bacillus subtilis. To achieve this, "stacking blocks" strategy developed rationally series LLPS-promoting for programming condensates. Through targeted recruitment biomolecules, our investigation demonstrates that effectively sequester biosynthetic pathways. We successfully harness this capability enhance biosynthesis 2'-fucosyllactose by 123.3%. Furthermore, find can specificity tailored enzyme fourfold, and increase N-acetylmannosamine titer 75.0%. Collectively, these results lay foundation endowed with multifunctional capacities.

Language: Английский

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Creating new-to-nature carbon fixation: A guide

Metabolic Engineering, Journal Year: 2023, Volume and Issue: 82, P. 12 - 28

Published: Dec. 29, 2023

Language: Английский

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Carbene-mediated gelatin and hyaluronic acid hydrogel paints with ultra adhesive ability for arthroscopic cartilage repair

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 273, P. 133122 - 133122

Published: June 13, 2024

Language: Английский

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Computationally-Aided and Polyketide Synthase-Based Controlled Synthesis of Polycyclopropanated Fuel Molecules

Published: Jan. 1, 2025

Reducing carbon emissions from aviation and long-distance transportation sectors requires the development of sustainable biofuels with suitable energy density, freezing point, other physical properties. We previously demonstrated biological production high polycyclopropanated fatty acids (POP-FAs, class I) using an iterative polyketide synthase (iPKS) pathway in a Streptomyces host. Here, we used computational model fuel properties to design POP-FA products that are better for biofuel applications than produced POP-FAs. Then, modified chain length cyclopropane ratio POP-FAs by vivo gene exchange, highlighting cyclopropanase (CP) catalysis be key engineering. Leveraging both natural engineered product diversity, demonstrate targeted new classes POP-FAs, namely shortened (class II) distinct positions, as well fully cyclopropane-saturated III). Compared I II predicted have superior point aviation, while III should energy-density. These precise controllable modifications structure open door bioproduction designer POP fuels.

Language: Английский

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Future of Enzymology—An Appraisal

Published: Jan. 1, 2025

Language: Английский

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