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更新于：2025-05-07

CYP51 (Yeast)

更新于：2025-05-07

基本信息

别名

CYP51 (Yeast)、CYPLI、Cytochrome P450 51

+ [2]

简介

Sterol 14alpha-demethylase that plays a critical role in the third module of ergosterol biosynthesis pathway, being ergosterol the major sterol component in fungal membranes that participates in a variety of functions (PubMed:105731, PubMed:369554). The third module or late pathway involves the ergosterol synthesis itself through consecutive reactions that mainly occur in the endoplasmic reticulum (ER) membrane (PubMed:32679672). Starting from lanosterol (lanosta-8,24-dien-3beta-ol), it catalyzes the three-step oxidative removal of the 14alpha-methyl group (C-32) of the sterol in the form of formate, and converts the sterol to 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol, which is critical for ergosterol biosynthesis (PubMed:105731, PubMed:3543000, PubMed:369554). Can demethylate substrates not intrinsic to yeast, such as eburicol (24-methylene-24,25-dihydrolanosterol) at a similar rate to lanosterol, and at a lower rate the 24,25-dihydrolanosterol (DHL) to 4,4-dimethyl-8,14-cholestadien-3beta-ol (PubMed:1872829, PubMed:3543000).

关联

项与 CYP51 (Yeast) 相关的药物

CYP51 inhibitors-4e(Instituto Politécnico Nacional)

靶点

CYP51 (Yeast)

作用机制

CYP51 (Yeast) 抑制剂

在研机构

Instituto Politecnico Nacional

原研机构-

在研适应症

真菌病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

CYP51 inhibitors-6i(Instituto Politécnico Nacional)

靶点

CYP51 (Yeast)

作用机制

CYP51 (Yeast) 抑制剂

在研机构

Instituto Politecnico Nacional

原研机构-

在研适应症

真菌病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

CYP51 inhibitors-6f(Instituto Politécnico Nacional)

靶点

CYP51 (Yeast)

作用机制

CYP51 (Yeast) 抑制剂

在研机构

Instituto Politecnico Nacional

原研机构-

在研适应症

真菌病

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 CYP51 (Yeast) 相关的临床结果

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100 项与 CYP51 (Yeast) 相关的转化医学

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0 项与 CYP51 (Yeast) 相关的专利（医药）

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315

项与 CYP51 (Yeast) 相关的文献（医药）

2025-01-02·Journal of Biomolecular Structure and Dynamics

Network pharmacology, molecular docking-driven, Qbd-Engineered antifungal in-situ gel loaded with voriconazole nanostructured lipid carriers

Article

作者: Tiwari, Abhishek ; Kumar, Manish ; Palaria, Binita ; Kumar, Neeraj ; Tiwari, Varsha ; Aslam, Ramsha

Fungal infections (FIs) affect majority of the population, but the current treatments face challenges in terms of their effectiveness. This study focused on specific fungal targets, including dihydrofolate reductase (DHFR), acetohydroxy-acid synthase (AHAS), farnesyltransferase and endoglucanase. The docking studies were conducted with the drug voriconazole (VCZ), comparing it with Fluconazole (FCZ) and Amphotericin B (ATB) against 11 protein data bank (PDB) IDs (IDYR, 3NZB, 6DEQ, 1KS5, 7T0C, 1FY4, 5AJH, 7R79, 6TZ6 and 6IDY). Molecular dynamics (MD) analysis, including RMSD, RMSF, PCA and FEL, confirmed the stability of VCZ. The solubility of VCZ was a problem, so nanostructured lipid carriers (NLCs) were developed to improve ocular penetration. VCF5 was the optimized formulation by using 3² full factorial design. VCZF5-NLCs were the best in terms of nanoparticle size (126.6 nm), Zeta potential (33.5 mV), drug content (DC; 97.38 ± 0.210), encapsulation efficiency (EE; 88.01 ± 0.272) and extended drug release. The results of the ex-vivo corneal diffusion study indicate that VCZ-NLC-loaded in-situ gel (VCZ-NLC-IG3) exhibited DC of 88.25% and drug entrapment (DE) of 74.2%. The results of the zone of inhibition indicated that VCZ-NLC-IG3 had superior efficacy compared to ATB. Network pharmacology showed VCZ interacts with the genes which are responsible for fungus ergosterol biosynthesis, including lanosterol 14-alpha demethylase inhibitors (ERG11), ergosterol biosynthesis protein 5 (ERG5), dimethylallyltransferase 2 (DIT2), ketosynthase (KCN), methylsterol monooxygenase (MSMO1), lamin B receptor (LBR), squalene epoxidase (SQLE), 3-hydroxy-3-methylglutaryl-coenzyme A Reductase (MGCR), 3-hydroxy-3-methylglutaryl-coenzyme A Synthase (HMGCS) and 3-keto-steroid reductase (HSD17B7). In conclusion, the optimized VCZ-loaded NLCs present a promising approach to treat ocular FIs.Communicated by Ramaswamy H. Sarma.

2024-12-16·Journal of Biomolecular Structure and Dynamics

Purification and structure elucidation of Penicillium chrysogenum derived antifungal compound with potential anti-Candida property: in silico and in vitro evidence

Article

作者: Ahmad, Sajjad ; Iqbal, Zafar ; Alharbi, Metab ; Alasmari, Abdullah F. ; Lutfullah, Ghosia ; Irfan, Muhammad ; Khattak, Saeed Ullah

Following preliminary bioactivity testing, the fungal strain identified as Penicillium crysogenum was cultured in a modified Czapec Yeast Broth medium (CYB) for the production of antifungal compounds. Several chromatographic techniques including HPLC were used to purify the fungal metabolites from the crude extract. The mass determination of the purified compound was performed using Water's LCMS system while the structure of the compound was elucidated using 400 and 500 Varian NMR machines. The chemical name of the purified compound is (2 R, 4S) -2, 4-dimethyl-4-((E)-2-((3S, 4S)-2, 4, 5-trihydroxy-3-methoxy-4-phenyl^-1, 2, 3, 4-tetrahydroquinolin-6-yl) vinyl) cyclohexanone with the chemical formula C₂₆H₃₁NO₅ and exact mass of 437.2. Molecular docking predicted compound docking score with dihydrofolate reductase enzyme and lanosterol 14α-demethylase enzyme as -8.1 kcal/mol and -9.8 kcal/mol respectively. Further, the compounds showed stable binding mode with the enzymes and reported robust binding energies. After insilico analysis, the compound with mass 437 was tested for its antifungal potential in vitro against two pathogenic yeast species (i.e. Candida albicans and Candida glaberata) using the agar tube diffusion method. Using sterile di-methyl sulfoxide (DMSO) the compound was prepared in four dose concentrations (100, 250, 500, 1000 µg mL^-1) and mixed with autoclaved semisolid Potato Dextrose Agar (PDA) medium in screw-capped test tubes labelled with the corresponding dose concentration. The fungal strains were inoculated on this medium and linear growth inhibition of the fungal strains was calculated using fluconazole as the control drug. The results from in vitro experiments were encouraging as at concentrations of 500 and 1000 μg mL^-1 the compound inhibited the growth of C. albicans by 17% and 38% while 19% and 41% inhibition were recorded against C. glaberata. The compound showed antifungal activity in silico and in vitro against both the Candida species and can act as a potent antifungal candidate in the future upon further investigation.Communicated by Ramaswamy H. Sarma.

2024-12-01·3 Biotech

Rational design of lanosterol 14α-demethylase for ergosterol biosynthesis in Saccharomyces cerevisiae

Article

作者: Zhou, Jingwen ; Qin, Zhijie ; Zeng, Weizhu ; Chen, Qihang ; Xu, Kangjie ; Wang, Xinglong ; Wei, Wenqian ; Liang, Ruixue

Ergosterol is widely used in skin care products and drug preparation. Lanosterol 14α-demethylase (Erg11p, 14DM, CYP51) is the rate-limiting enzyme for the biosynthesis of various steroid compounds in Saccharomyces cerevisiae. Herein, Erg11p was engineered to extend the in vivo catalytic half-life and increase the turnover rate. Single mutations resulting in lower folding energy were selected, and mutant P201H had an ergosterol yield of 576.9 mg·L^-1. Through consensus design, single mutations resulting in higher sequence identity to homologs were tested and mutant K352L had an ergosterol yield of 677.9 mg·L^-1. The key residues for substrate binding were confirmed via alanine scanning mutagenesis and mutant F384A had an ergosterol yield of 657.8 mg·L^-1. Molecular dynamics (MD) simulation was conducted to investigate the contributions of pocket residues and eight residues were found to engage in weak interactions with lanosterol. Saturation mutagenesis was applied to these residues to enhance binding to lanosterol, and mutant F384E had an ergosterol yield of 733.8 mg·L^-1. Meanwhile, MD simulations were conducted to assess the impact of mutant F384E on enzyme activity. The results consistently showed that single point mutation F384E had the greatest effect, outperforming the combination mutations. Batch fermentation increased the ergosterol yield of mutant F384E to 3067.5 mg·L^-1, the highest reported to date. The successful engineering of Erg11p may pave the way for industrial-scale production of ergosterol and other steroids.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13205-024-04136-x.