New Trends and Future Opportunities in the Enzymatic Formation of C−C, C−N, and C−O bonds

ChemBioChem, Год журнала: 2021, Номер 23(6)

Опубликована: Ноя. 2, 2021

Organic chemistry provides society with fundamental products we use daily. Concerns about the impact that chemical industry has over environment is propelling major changes in way manufacture chemicals. Biocatalysis offers an alternative to other synthetic approaches as it employs enzymes, Nature's catalysts, carry out transformations. Enzymes are biodegradable, come from renewable sources, operate under mild reaction conditions, and display high selectivities processes they catalyse. As a highly multidisciplinary field, biocatalysis benefits advances different areas, developments fields of molecular biology, bioinformatics, engineering have accelerated extension range available transformations (E. L. Bell et al., Nat. Rev. Meth. Prim. 2021, 1, 1-21). Recently, surveyed expansion scope via enzyme discovery protein (J. R. Marshall Tetrahedron 82, 131926). Herein, focus on novel enzymes currently broad community for construction new C-C, C-N C-O bonds, purpose providing non-specialist tools chiral sustainable synthesis.

Язык: Английский

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Branching and converging pathways in fungal natural product biosynthesis

Fungal Biology and Biotechnology, Год журнала: 2022, Номер 9(1)

Опубликована: Март 7, 2022

Abstract In nature, organic molecules with great structural diversity and complexity are synthesized by utilizing a relatively small number of starting materials. A synthetic strategy adopted nature is pathway branching, in which common biosynthetic intermediate transformed into different end products. natural product can also be the fusion two or more precursors generated from separate metabolic pathways. This review article summarizes several representative branching converging pathways fungal biosynthesis to illuminate how fungi capable synthesizing diverse array

Язык: Английский

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Discovery of branching meroterpenoid biosynthetic pathways in Aspergillus insuetus: involvement of two terpene cyclases with distinct cyclization modes

Chemical Science, Год журнала: 2022, Номер 13(35), С. 10361 - 10369

Опубликована: Янв. 1, 2022

Branching meroterpenoid biosynthetic pathways were discovered in the fungus Aspergillus insuetus CBS 107.25, which two terpene cyclases, InsA7 and InsB2, accept same substrate but generate distinctly cyclized products.

Язык: Английский

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Evolution of a Strategy for the Unified, Asymmetric Total Syntheses of DMOA-Derived Spiromeroterpenoids

The Journal of Organic Chemistry, Год журнала: 2024, Номер 89(17), С. 11891 - 11908

Опубликована: Авг. 12, 2024

DMOA-derived spiromeroterpenoids are a group of natural products with complex structures and varied biological activities. Recently, we reported the first enantioselective total synthesis five based on fragment coupling strategy. This full account describes details strategy evolution that culminated in successful syntheses targeted products. Although our alkylative dearomatization methodology was unable to deliver desired spirocyclic first-generation approach, second-generation approach oxidative [3 + 2] cycloaddition produced asnovolin H core along several dimers. Challenges finally led us develop third generation, non-dearomatization construct conserved, sterically hindered bis-neopentyl linkage through 1,2-addition. To enable scalable access products, refined, multigram-scale partners developed. A series stereoselective transformations were developed judicious choice reagents conditions. Finally, modular spirocycle construction logic demonstrated small library spiromeroterpenoid analogues.

Язык: Английский

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Enantioselective Total Synthesis of Berkeleyone A and Preaustinoids

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(27), С. 14869 - 14874

Опубликована: Апрель 16, 2021

Abstract Herein we report the first enantioselective total synthesis of 3,5‐dimethylorsellinic acid‐derived meroterpenoids (−)‐berkeleyone A and its five congeners ((−)‐preaustinoids A, A1, B, B1, B2) in 12–15 steps, starting from commercially available 2,4,6‐trihydroxybenzoic acid hydrate. Based upon recognition latent symmetry within D‐ring, our convergent features two critical reactions: 1) a symmetry‐breaking, diastereoselective dearomative alkylation to assemble entire carbon core, 2) Sc(OTf) 3 ‐mediated sequential Krapcho dealkoxycarbonylation/carbonyl α‐ tert ‐alkylation forge intricate bicyclo[3.3.1]nonane framework. We also conducted preliminary biomimetic investigations uncovered series rearrangements (α‐ketol, α‐hydroxyl‐β‐diketone, etc.) responsible for diversification into preaustinoid congeners.

Язык: Английский

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Application of Crystalline Matrices for the Structural Determination of Organic Molecules

ACS Central Science, Год журнала: 2021, Номер 7(3), С. 406 - 414

Опубликована: Фев. 17, 2021

While single-crystal X-ray diffraction (SC-XRD) is one of the most powerful structural determination techniques for organic molecules, requirement obtaining a suitable crystal analysis limits its applicability, particularly liquids and amorphous solids. The emergent use preformed porous crystalline matrices that can absorb compounds stabilize them via host–guest interactions observation SC-XRD offers way to overcome this hindrance. A topical current discussion in chemistry crystallo compounds, with particular focus on absolute structure chiral presented. Preformed are covered include metal–organic frameworks (MOFs) as used sponge method, polyhedra (MOPs, coordination cages), materials (POMs)/porous molecular crystals (POMCs), biological scaffolds. An outlook perspective technology future directions provided.

Язык: Английский

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Dissection of the Catalytic Mechanisms of Transmembrane Terpene Cyclases Involved in Fungal Meroterpenoid Biosynthesis

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(30)

Опубликована: Май 30, 2023

Pyr4-family terpene cyclases are noncanonical transmembrane involved in the biosynthesis of microbial meroterpenoids and catalyze diverse cyclization reactions. Despite ubiquity microorganisms, their three-dimensional structures have never been experimentally determined. Herein, we focused on AdrI, enzyme for andrastin A pathway, its homologues, performed a series mutational experiments using AlphaFold2-generated structures. Intriguingly, found that AdrI InsA7, which both accept same substrate, use different amino acid residues initiation cascade. Furthermore, obtained several variants with altered product selectivity, one dominantly yielded new meroterpenoid species. Collectively, our study provides important insights into catalytic functions will facilitate engineering these enzymes.

Язык: Английский

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Cyclization diversity of meroditerpenoids from endophytic fungi of medicinal plants driven by synthetic biology strategies

Science of Traditional Chinese Medicine, Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

Abstract Background Medicinal plants rich in endophytic fungi are a significant source of natural lead compounds. Meroterpenoids, which hybrid products originating from partially terpenoid pathways, exhibit impressive structural complexity and substantial potential as drug candidates. The diversity meroterpenoids is largely attributed to the functional cyclases, generate variety compounds with different ring systems. This enzymatic versatility underscores biochemical their invaluable role discovery. Objective aim study was investigate Paris polyphylla var. yunnanensis facilitating diverse cyclization modifications meroditerpenoids through four terpene cyclases (TCs) Pyr4 family. Methods utilized recombinant strategy successfully reconstruct distinct TCs heterologous host, Aspergillus oryzae NSAR1. characterization resulting secondary metabolites performed using mass spectrometry NMR techniques. Results substitution endophytes felis 0260 Fusarium graminearum 1962 hydrophobic intermediates 1 2 , led production sartorypyrone C ( 3 ) new compound, 4′-methylchevalone E 4 ), respectively. demonstrates critical enhancing diversity. Conclusions These findings provide valuable insights into compatibility pathway combinations interchangeability derived medicinal plants, advanced understanding meroditerpenoid biosynthesis highlighted importance

Язык: Английский

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Fungi: Pioneers of chemical creativity – Techniques and strategies to uncover fungal chemistry

IMA Fungus, Год журнала: 2025, Номер 16

Опубликована: Март 7, 2025

Natural product discovery from fungi for drug development and description of novel chemistry has been a tremendous success. This success is expected to accelerate even further, owing the advent sophisticated technical advances that recently led an unparalleled biodiversity in fungal kingdom. review aims give overview on i) important secondary metabolite-derived drugs or leads, ii) discuss analytical strategic framework how natural lead identification transformed earlier days present, iii) knowledge biology facilitates new compounds, iv) point out endeavors understanding metabolite order systematically explore genomes by utilizing synthetic biology. An outlook given, underlining necessity collaborative cooperative scenario harness full potential metabolome.

Язык: Английский

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Peculiarities of meroterpenoids and their bioproduction

Applied Microbiology and Biotechnology, Год журнала: 2021, Номер 105(10), С. 3987 - 4003

Опубликована: Май 1, 2021

Язык: Английский

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