The bacterial cytochrome P450 (CYP) CYP125 enzymes can competitively oxidise sitosterol in the presence of cholesterol

Doherty, Daniel Z; Ghith, Amna; Ho, A. D.; Voss, James J. De; Bell, Stephen

doi:10.1039/d3cc02312e

Chem. Commun.

2023

DOI: 10.1039/d3cc02312e

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The bacterial cytochrome P450 (CYP) CYP125 enzymes can competitively oxidise sitosterol in the presence of cholesterol

Daniel Z Doherty

Amna Ghith

A. D. Ho

et al.

Abstract: Cholesterol catabolism is an important survival mechanism for the pathogenic Mycobacterium tuberculosis. Various other mycobacteria degrade not only cholesterol but plant sterols such as sitosterol and campesterol. In this work...

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Cited by 4 publications

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“…The cytochrome P450 CYP125 enzyme family from pathogenic Mycobacterium tuberculosis , that are critical for cholesterol catabolism, have been shown to oxidise plant sterols such as sitosterol 30 . 30 In particular, CYP125A1 was shown to oxidise sitosterol to 26-hydroxysitosterol (Scheme 2), even in the presence of cholesterol.…”

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Hill,

Sutherland

2023

Nat. Prod. Rep.

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confidence: 99%

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Hill,

Sutherland

2023

Nat. Prod. Rep.

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Selective Partial Reduction of Nitroarenes to the Hydrazoarene Catalyzed by Amine‐Modified Ordered Mesoporous Silica Immobilized Ionic Liquid (OMSIIL) Stabilised RuNPs

Doherty,

Knight,

Alharbi

et al. 2024

ChemCatChem

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Ruthenium nanoparticles stabilised by an amine‐modified Ordered Mesoporous Silica Immobilized Ionic Liquid (OMSIIL) are efficient catalysts for the partial reduction of nitrobenzene to hydrazobenzene with 100% selectivity as well as the complete reduction to aniline. High selectivity for the partial reduction of nitrobenzene to hydrazobenzene was obtained when the reaction was conducted in ethanol with 0.5 mol% catalyst and NaBH4 as the hydrogen donor whereas aniline was obtained as the sole product in water when dimethylamine borane (DMAB) was used as the hydrogen donor. Interestingly, while a range of electron poor nitroarenes were reduced to the corresponding hydrazoarene with high selectivities and good conversions, nitroarenes substituted with electron donating groups resulted in complete reduction to the aniline. Composition‐time profiles suggest that reductions conducted in ethanol with sodium borohydride occur via the condensation pathway while those conducted in water using dimethylamine borane as the hydrogen source may well go via the direct pathway. This is the first example of the selective reduction of nitrobenzene to hydrazobenzene using a ruthenium nanoparticle‐based catalyst and the initial TOF of 320 mol nitrobenzene converted mol Ru‐1 h‐1 is markedly higher than previous literature reports.

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Bacterial Acyl Homoserine Lactones Triggered Non‐Native Substrate Hydroxylation Catalyzed by Directed‐Evolution‐Derived Cytochrome P450BM3 Mutants

Yokoyama,

Ariyasu,

Karasawa

et al. 2024

ChemCatChem

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We report the directed evolution of cytochrome P450BM3 to efficiently utilise the bacterial quorum sensing signalling molecule N‐decanoyl homoserine lactone (C10‐HSL) as an effective decoy molecule. This represents the first important step in our endeavour to develop of a self‐sufficient decoy‐molecule system in whole‐cells that only necessitates the addition of culture medium and substrate to realise the hydroxylation of non‐native substrates. Following five rounds of directed evolution, mutant P450BM3, in the presence of C10‐HSL, catalysed the hydroxylation of benzene at a rate of 475 min−1, the highest turnover rate recorded for any P450 enzyme, and achieving a 46% yield in a whole‐cell reaction system. High‐resolution X‐ray crystal structure analysis of a series of mutants narrates the directed evolution process, revealing how C10‐HSL is fixed in the binding pocket to permit binding of non‐native substrates. Finally, introduction of the C10‐HSL synthase gene ExpI into E. coli, enabled the in‐situ production of C10‐HSL, realising, for the first time, the hydroxylation of non‐native substrates without the need for the laborious synthesis and addition of decoy molecules.

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The bacterial cytochrome P450 (CYP) CYP125 enzymes can competitively oxidise sitosterol in the presence of cholesterol

Abstract: Cholesterol catabolism is an important survival mechanism for the pathogenic Mycobacterium tuberculosis. Various other mycobacteria degrade not only cholesterol but plant sterols such as sitosterol and campesterol. In this work...

Cited by 4 publications

References 38 publications

Hot off the Press

Hot off the Press

Selective Partial Reduction of Nitroarenes to the Hydrazoarene Catalyzed by Amine‐Modified Ordered Mesoporous Silica Immobilized Ionic Liquid (OMSIIL) Stabilised RuNPs

Bacterial Acyl Homoserine Lactones Triggered Non‐Native Substrate Hydroxylation Catalyzed by Directed‐Evolution‐Derived Cytochrome P450BM3 Mutants

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