The characterisation of two members of the cytochrome P450 CYP150 family: CYP150A5 and CYP150A6 from Mycobacterium marinum

Child, Stella A.; Flint, Kate L.; Bruning, John B.; Bell, Stephen

doi:10.1016/j.bbagen.2019.02.016

Cited by 4 publications

(5 citation statements)

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“…The bacterial CYP150A5 was shown to bind various norisoprenoids and terpenoids and could regioselectively hydroxylate β-ionol. 6 Medicago truncatula CYP72A67 is a 2βhydroxylase, which revealed hydroxylase activity for C-2 of oleanolic acid and hederagenin. 7 However, the oxidative capabilities of human CYP enzymes on nondrug natural products have not been investigated in detail.…”

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confidence: 99%

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Experimental and Computational Studies on the Biotransformation of Pseudopyronines with Human Cytochrome P450 CYP4F2

Lotfy

et al. 2022

J. Nat. Prod.

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The secondary metabolite pseudopyronine B, isolated from Pseudomonas mosselii P33, was biotransformed by human P450 enzymes, heterologously expressed in the fission yeast Schizosaccharomyces pombe. Small-scale studies confirmed that both CYP4F2 and CYP4F3A were capable of oxidizing the substrate, with the former achieving a higher yield. In larger-scale studies using CYP4F2, three new oxidation products were obtained, the structures of which were elucidated by UV–vis, 1D and 2D NMR, and HR-MS spectroscopy. These corresponded to hydroxylated, carboxylated, and ester derivatives (1–3) of pseudopyronine B, all of which had been oxidized exclusively at the ω-position of the C-6 alkyl chain. In silico homology modeling experiments highlighted key interactions between oxygen atoms of the pyrone ring and two serine residues and a histidine residue of CYP4F2, which hold the substrate in a suitable orientation for oxidation at the terminus of the C-6 alkyl chain. Additional modeling studies with all three pseudopyronines revealed that the seven-carbon alkyl chain of pseudopyronine B was the perfect length for oxidation, with the terminal carbon lying close to the heme iron. The antibacterial activity of the substrates and three oxidation products was also assessed, revealing that oxidation at the ω-position removes all antimicrobial activity. This study both increases the range of known substrates for human CYF4F2 and CYP4F3A enzymes and demonstrates their utility in producing additional natural product derivatives.

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confidence: 99%

“…CYPs monooxygenation reactions can also be applied as a method for the structural modification of natural products. The bacterial CYP150A5 was shown to bind various norisoprenoids and terpenoids and could regioselectively hydroxylate β-ionol .…”

mentioning

confidence: 99%

Experimental and Computational Studies on the Biotransformation of Pseudopyronines with Human Cytochrome P450 CYP4F2

Lotfy

et al. 2022

J. Nat. Prod.

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“…EuI1c were primarily related to P450s from other Frankia species, a few are related to known species from other organisms. For example, CYP147F19 was related to CYP147G1 (45%, sequence identity) and CYP150A20 was related to CYP150A6 (55%), both of which are from Mycobacterium marinum M. [30][31][32] Of the 68 P450 superfamily members 21 belonged to the CYP189 family (11 members of A, 6 members of B and 2 members of the C subfamilies and one each from those of E and F). Table S3 for more details).…”

Section: Analysis Of the P450 Content Of Frankia Sp Eui1cmentioning

confidence: 99%

“…For example, CYP150A6 and CYP150A5, both from Mycobacterium marinum species share 50% and 55% amino acid sequence identity, respectively with CYP150A20 (Table 5). [32] The three other CYP150A subfamily members of Frankia sp. EuI1c shared 50-51% (A21, A22 and A23) amino acid sequence identity to CYP150A20 ( Table 5).…”

Section: Investigation Of Substrate Binding To Cyp150a20mentioning

confidence: 99%

“…Members of the CYP150 family has been reported to oxidise polycyclic aromatic hydrocarbons and CYP150A5 from M. marinum has been demonstrated to bind a range of compounds including norisoprenoids and terpenoid based substrates including the aromatic sesquiterpene guaiazulene (1,4-dimethyl-7-isopropylazulene). [32,59] Therefore CYP150A20 was screened with a range of aromatic hydrocarbons, fatty acids, monoterpenoids and steroids (Figure 3). Steroids, such as testosterone, and fatty acids did not induce any spin state shift.…”

Section: Investigation Of Substrate Binding To Cyp150a20mentioning

confidence: 99%

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Analysis and preliminary characterisation of the cytochrome P450 monooxygenases from Frankia sp. EuI1c (Frankia inefficax sp.)

Lau

Nelson

Bell

2019

Archives of Biochemistry and Biophysics

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A comparison of steroid and lipid binding cytochrome P450s from Mycobacterium marinum and Mycobacterium tuberculosis

Child

Ghith

Bruning

et al. 2020

Journal of Inorganic Biochemistry

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The characterisation of two members of the cytochrome P450 CYP150 family: CYP150A5 and CYP150A6 from Mycobacterium marinum

Cited by 4 publications

References 67 publications

Experimental and Computational Studies on the Biotransformation of Pseudopyronines with Human Cytochrome P450 CYP4F2

Experimental and Computational Studies on the Biotransformation of Pseudopyronines with Human Cytochrome P450 CYP4F2

Analysis and preliminary characterisation of the cytochrome P450 monooxygenases from Frankia sp. EuI1c (Frankia inefficax sp.)

A comparison of steroid and lipid binding cytochrome P450s from Mycobacterium marinum and Mycobacterium tuberculosis

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