Engineered and total biosynthesis of fungal specialized metabolites

Nature Reviews Chemistry, Год журнала: 2024, Номер 8(1), С. 61 - 78

Опубликована: Янв. 3, 2024

Язык: Английский

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The protective effect of natural medicines in rheumatoid arthritis via inhibit angiogenesis

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Май 31, 2024

Rheumatoid arthritis is a chronic immunological disease leading to the progressive bone and joint destruction. Angiogenesis, accompanied by synovial hyperplasia inflammation underlies Delaying or even blocking angiogenesis has emerged as an important target of RA treatment. Natural medicines long history treating RA, numerous reports have suggested that natural strong inhibitory activity on angiogenesis, thereby improving progression RA. could regulate following signaling pathways: HIF/VEGF/ANG, PI3K/Akt pathway, MAPKs NF-κB PPARγ JAK2/STAT3 etc., inhibiting angiogenesis. Tripterygium wilfordii Hook. f. (TwHF), sinomenine, total glucoside Paeonia lactiflora Pall. Are currently most representative all products worthy development utilization. In this paper, main factors affecting were discussed different types inhibit systematically summarized. Their specific anti-angiogenesis mechanisms are also reviewed which aiming provide new perspective options for management targeting

Язык: Английский

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Biocatalytic Steroidal 9α‐Hydroxylation and Fragmentation Enable the Concise Chemoenzymatic Synthesis of 9,10‐Secosteroids

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(16)

Опубликована: Фев. 20, 2024

Abstract 9,10‐Secosteroids are an important group of marine steroids with diverse biological activities. Herein, we report a chemoenzymatic strategy for the concise, modular, and scalable synthesis ten naturally occurring 9,10‐secosteroids from readily available in three to eight steps. The key feature lies utilizing Rieske oxygenase‐like 3‐ketosteroid 9α‐hydroxylase (KSH) as biocatalyst achieve efficient C9−C10 bond cleavage A‐ring aromatization tetracyclic through 9α‐hydroxylation fragmentation. With synthesized 9,10‐secosteroides, structure–activity relationship was evaluated based on bioassays terms previously unexplored anti‐infective activity. This study provides experimental evidence support hypothesis that biosynthetic pathway which formed nature shares similar fragmentation cascade. In addition development biomimetic approach 9,10‐secosteroid synthesis, this highlights great potential strategies chemical synthesis.

Язык: Английский

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The role of biocatalysis in the asymmetric synthesis of alkaloids – an update

RSC Advances, Год журнала: 2021, Номер 11(45), С. 28223 - 28270

Опубликована: Янв. 1, 2021

This review article discusses developments in the chemo-enzymatic synthesis of alkaloids since 2013, showcasing how modern methods organic and biocatalysis are combined to establish novel routes towards these important natural products.

Язык: Английский

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Properties and Mechanisms of Flavin-Dependent Monooxygenases and Their Applications in Natural Product Synthesis

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(5), С. 2622 - 2622

Опубликована: Фев. 27, 2022

Natural products are usually highly complicated organic molecules with special scaffolds, and they an important resource in medicine. structures produced by enzymes, this is still a challenging research field, its mechanisms requiring detailed methods for elucidation. Flavin adenine dinucleotide (FAD)-dependent monooxygenases (FMOs) catalyze many oxidation reactions chemo-, regio-, stereo-selectivity, involved the synthesis of natural products. In review, we introduce different FMOs, classical FAD (C4a)-hydroperoxide as major oxidant. We also summarize difference between FMOs cytochrome P450 (CYP450) emphasizing advantages their specificity substrates. Finally, present examples FMO-catalyzed Based on these explanations, review will expand our knowledge powerful well implementation effective tools biosynthesis.

Язык: Английский

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Discovery of a Fungal P450 with an Unusual Two-Step Mechanism for Constructing a Bicyclo[3.2.2]nonane Skeleton

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(12), С. 8716 - 8726

Опубликована: Март 14, 2024

The successful biomimetic or chemoenzymatic synthesis of target natural products (NPs) and their derivatives relies on enzyme discovery. Herein, we discover a fungal P450 BTG5 that can catalyze the formation bicyclo[3.2.2]nonane structure through an unusual two-step mechanism dimerization cyclization in biosynthesis beticolin 1, whose skeleton connects anthraquinone moiety xanthone moiety. Further investigation reveals BTG5-T318 not only determines substrate selectivity but also alters catalytic reactions, which allows separation reaction to two individual steps, thereby understanding its mechanism. It first heterodimerization undergoes common oxidation process for P450s, while second uncommon formal redox-neutral step is proved as redox-mediated reaction, has never been reported. Therefore, this work advances our P450-catalyzed reactions paves way expansion diversity class NPs synthetic biology.

Язык: Английский

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Chemoenzymatic total synthesis of alchivemycin A

Nature Synthesis, Год журнала: 2024, Номер 3(9), С. 1124 - 1133

Опубликована: Июнь 25, 2024

Язык: Английский

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Carbocycloaddition strategies for troponoid synthesis

Tetrahedron, Год журнала: 2022, Номер 130, С. 133175 - 133175

Опубликована: Дек. 1, 2022

Язык: Английский

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Microbial Production of Human Milk Oligosaccharides

Molecules, Год журнала: 2023, Номер 28(3), С. 1491 - 1491

Опубликована: Фев. 3, 2023

Human milk oligosaccharides (HMOs) are complex nonnutritive sugars present in human milk. These possess prebiotic, immunomodulatory, and antagonistic properties towards pathogens therefore important for the health well-being of newborn babies. Lower prevalence breastfeeding around globe, rising popularity nutraceuticals, low availability HMOs have inspired efforts to develop economically feasible efficient industrial-scale production platforms HMOs. Recent progress synthetic biology metabolic engineering tools has enabled microbial systems be a system In this regard, model organism Escherichia coli emerged as preferred platform. Herein, we summarize remarkable discuss challenges future opportunities unraveling scope We focus on five that been approved their commercialization.

Язык: Английский

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Advanced Technologies for Large Scale Supply of Marine Drugs

Marine Drugs, Год журнала: 2025, Номер 23(2), С. 69 - 69

Опубликована: Фев. 7, 2025

Marine organisms represent a source of unique chemical entities with valuable biomedical potentialities, broad diversity, and complexity. It is essential to ensure reliable sustainable supply marine natural products (MNPs) for their translation into commercial drugs other products. From structural point view few exceptions, MNPs pharmaceutical importance derive from the so-called secondary metabolism organisms. When production strategies rely on macroorganisms, harvesting or culturing coupled extraction procedures frequently remain only alternative producing these compounds an industrial scale. Their can often be implemented laboratory scale cultures bacterial, fungal, microalgal sources. However, diverse approach, combining traditional methods modern synthetic biology biosynthesis strategies, must considered invertebrate MNPs, as they are usually naturally accumulated in very small quantities. This review offers comprehensive examination various addressing challenges related supply, synthesis, scalability. also underscores recent biotechnological advancements that likely transform current industrial-scale manufacturing pharmaceuticals derived

Язык: Английский

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