Tetrahedron Chem, Journal Year: 2024, Volume and Issue: unknown, P. 100112 - 100112
Published: Nov. 1, 2024
Language: Английский
ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(8), P. 6211 - 6216
Published: April 9, 2024
Fluorine is a unique element with important roles in medicinal chemistry, agrochemistry, and materials chemistry. The fluoroethyl group an fluoroalkyl functional unit that widely used clinical drugs, 19F probes 18F PET diagnostic drugs. Chemo- regioselective fluoroethylation difficult chemical synthesis. To date, no enzymatic reaction for selective has been reported. Based on the widespread natural methyl donor S-adenosine-l-methionine (SAM), we designed synthesized SAM analogue (FEt-SAM). A stability study revealed FEt-SAM was very labile under physiological conditions gave fluorine-elimination product vinyl-SAM. We circumvented this problem by replacing S Se to give Se-adenosyl-l-selenomethionine (FEt-SeAM). By using halide methyltransferase (HMT) its mutant situ production of FEt-SeAM, created cascade reactions HMT methyltransferases fluoroethylated several O-, N-, S-, C-nucleophiles. For did not recognize FEt-SeAM well, such as DnrK NovO, simple mutagenesis conserved hydrophobic residues (Leu Ile) binding pocket smaller amino acids significantly increased activities. Therefore, have provided useful tool late-stage products This method could also be enzymatically prepare NMR tests.
Language: Английский
Citations
8
Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(16)
Published: Feb. 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.
Language: Английский
Citations
5
Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(27), P. 18722 - 18729
Published: June 29, 2024
Methylation, a widely occurring natural modification serving diverse regulatory and structural functions, is carried out by myriad of S-adenosyl-l-methionine (AdoMet)-dependent methyltransferases (MTases). The AdoMet cofactor produced from l-methionine (Met) ATP family multimeric methionine adenosyltransferases (MAT). To advance mechanistic functional studies, strategies for repurposing the MAT MTase reactions to accept extended versions transferable group corresponding precursors have been exploited. Here, we used structure-guided engineering mouse MAT2A enable biocatalytic production an analogue, Ado-6-azide, synthetic S-(6-azidohex-2-ynyl)-l-homocysteine (N3-Met). Three engineered variants showed catalytic proficiency with analogues supported DNA derivatization in cascade M.TaqI variant DNMT1 both absence presence competing Met. We then installed two as MAT2A-DNMT1 cascades embryonic stem cells using CRISPR-Cas genome editing. resulting cell lines maintained normal viability methylation levels Dnmt1-dependent azide tags upon exposure N3-Met physiological This first time demonstrates genetically stable system biosynthetic which enables mild metabolic labeling DNMT-specific methylome live mammalian cells.
Language: Английский
Citations
4
Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown
Published: March 21, 2025
Synthetic biology has played an important role in the renaissance of natural products research during post-genomics era. The development and integration new tools have transformed workflow product discovery engineering, generating multidisciplinary interest field. In this review, we summarize recent developments biosynthesis from three different aspects. First, advances bioinformatics, experimental, analytical to identify associated with predicted biosynthetic gene clusters (BGCs) will be covered. This followed by extensive review on heterologous expression bacterial, fungal plant organisms. native host-independent paradigm identification, pathway characterization, enzyme is where synthetic most prominent role. Lastly, strategies engineer pathways for structural diversification complexity generation discussed, including assembly-line megasynthase precursor-directed modification, combinatorial biosynthesis.
Language: Английский
Citations
0
Biochemistry (Moscow), Journal Year: 2025, Volume and Issue: 90(S1), P. S105 - S134
Published: Feb. 1, 2025
Language: Английский
Citations
0
European Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 27(17)
Published: March 29, 2024
Abstract Organofluorine compounds find extensive application in the fields of agrochemicals, pharmaceuticals, materials science, and molecular imaging. Introducing fluorine atoms can provide organic with unique physicochemical properties or improve their biological activity. Although significant progress has been made chemical synthesis fluorine‐containing compounds, achieving selective fluorination under mild conditions remains extremely challenging. biocatalytic approaches organofluorine chemistry is an important strategy given high efficiency, selectivity, environmental friendliness. In this review, we present discovery fluorinated natural products fluorinases, crystal structure directed evolution a focus on recent advances enzymatic years. It hoped that review will help to promote field compound synthesis.
Language: Английский
Citations
3
Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 5, 2024
The trifluoromethyl (-CF
Language: Английский
Citations
2
ChemMedChem, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 14, 2024
The success of new therapeutic modalities relies on advancements in synthetic chemistry to produce compounds for evaluation throughout the drug discovery process. use non-canonical amino acids (ncAAs) allows properties peptide drugs be modified and optimised beyond defined characteristics 20 proteogenic acids. Synthesis ncAAs can either through a bespoke chemical synthesis, or directly from parent compound - using traditional reagents enzymes achieve desired modification. This review will highlight recent enzymatic functionalisation variety ncAAs.
Language: Английский
Citations
0
Critical Reviews in Microbiology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 19
Published: Dec. 1, 2024
Nucleos(t)ide analogs constitute a diverse group of compounds derived from nucleosides and nucleotides, playing crucial role in various biological processes. These exhibit wide range applications, including their use as additives, antiviral, anticancer agents, which makes them valuable food medical research. In this review, we will explore the applications nucleos(t)ide across different fields discuss latest advances engineering optimization strategies aimed at improving production efficiency tailoring properties for specific purposes. The article focuses on design microbial cell factories critical analogs. By leveraging biosynthesis pathways employing such metabolic engineering, researchers are optimizing synthesis This enhances both yield diversity analogs, leading to creation novel with enhanced bioactivity therapeutic potential. Consequently, these efforts driving significant advancements drug discovery biotechnology.
Language: Английский
Citations
0
Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(16)
Published: Feb. 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.
Language: Английский
Citations
0