Engineering CYP153A(M.aq) to Oxyfunctionalize its Inhibitor
Dodecylamine Using a LC/MS Based Rapid Flow Analysis Screening

J 2022

Engineering CYP153A(M.aq) to Oxyfunctionalize its Inhibitor Dodecylamine Using a LC/MS Based Rapid Flow Analysis Screening

RAPP, Lea R.; Sérgio Manuel MARQUES; Bernd NEBEL; Jiří DAMBORSKÝ; Bernhard HAUER et al.

Základní údaje

Originální název

Engineering CYP153A(M.aq) to Oxyfunctionalize its Inhibitor Dodecylamine Using a LC/MS Based Rapid Flow Analysis Screening

Autoři

RAPP, Lea R.; Sérgio Manuel MARQUES; Bernd NEBEL; Jiří DAMBORSKÝ a Bernhard HAUER

Vydání

ChemCatChem, WEINHEIM, WILEY-V C H VERLAG GMBH, 2022, 1867-3880

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10403 Physical chemistry

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.500

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/22:00126696

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

biocatalysis; cytochrome P450; docking; enzyme engineering; molecular dynamics

Štítky

14314010, 143180, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 11. 6. 2025 07:56, Mgr. Michaela Hylsová, Ph.D.

Anotace

V originále

The catalytic space of the P450 monooxygenase CYP153A(M.aq) was opened from a terminal (omega-) fatty acid hydroxylase to a catalyst capable of performing omega-hydroxylation of dodecylamine, which is a potent inhibitor for the wild-type enzyme. A simple screening method named Rapid-flow Analysis of Product Peaks (RAPP) was established and applied to measure saturation libraries directly from a 96-deepwell plate in 36 seconds per sample. The obtained variants are less inhibited by the amine, although concurrently show less affinity towards the acid. Molecular modelling and molecular dynamics simulations showed significant effects of the mutations on the substrate tunnel architectures.

Návaznosti

EF17_043/0009632, projekt VaV

Název: CETOCOEN Excellence

LM2018140, projekt VaV

Název: e-Infrastruktura CZ (Akronym: e-INFRA CZ)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, e-Infrastruktura CZ

90121, velká výzkumná infrastruktura

Název: RECETOX RI

Citovat

RAPP, Lea R.; Sérgio Manuel MARQUES; Bernd NEBEL; Jiří DAMBORSKÝ a Bernhard HAUER. Engineering CYP153A(M.aq) to Oxyfunctionalize its Inhibitor Dodecylamine Using a LC/MS Based Rapid Flow Analysis Screening. ChemCatChem. WEINHEIM: WILEY-V C H VERLAG GMBH, 2022, roč. 14, č. 6, s. 1-5. ISSN 1867-3880. Dostupné z: https://doi.org/10.1002/cctc.202101648.

@article{2218244,
   author = {Rapp, Lea R. and Marques, Sérgio Manuel and Nebel, Bernd and Damborský, Jiří and Hauer, Bernhard},
   article_location = {WEINHEIM},
   article_number = {6},
   doi = {https://doi.org/10.1002/cctc.202101648},
   keywords = {biocatalysis; cytochrome P450; docking; enzyme engineering; molecular dynamics},
   language = {eng},
   issn = {1867-3880},
   journal = {ChemCatChem},
   title = {Engineering CYP153A(M.aq) to Oxyfunctionalize its Inhibitor Dodecylamine Using a LC/MS Based Rapid Flow Analysis Screening},
   url = {https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cctc.202101648},
   volume = {14},
   year = {2022}
}

TY  - JOUR
ID  - 2218244
AU  - Rapp, Lea R. - Marques, Sérgio Manuel - Nebel, Bernd - Damborský, Jiří - Hauer, Bernhard
PY  - 2022
TI  - Engineering CYP153A(M.aq) to Oxyfunctionalize its Inhibitor Dodecylamine Using a LC/MS Based Rapid Flow Analysis Screening
JF  - ChemCatChem
VL  - 14
IS  - 6
SP  - 1-5
EP  - 1-5
PB  - WILEY-V C H VERLAG GMBH
SN  - 18673880
KW  - biocatalysis
KW  - cytochrome P450
KW  - docking
KW  - enzyme engineering
KW  - molecular dynamics
UR  - https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cctc.202101648
N2  - The catalytic space of the P450 monooxygenase CYP153A(M.aq) was opened from a terminal (omega-) fatty acid hydroxylase to a catalyst capable of performing omega-hydroxylation of dodecylamine, which is a potent inhibitor for the wild-type enzyme. A simple screening method named Rapid-flow Analysis of Product Peaks (RAPP) was established and applied to measure saturation libraries directly from a 96-deepwell plate in 36 seconds per sample. The obtained variants are less inhibited by the amine, although concurrently show less affinity towards the acid. Molecular modelling and molecular dynamics simulations showed significant effects of the mutations on the substrate tunnel architectures.
ER  -

RAPP, Lea R.; Sérgio Manuel MARQUES; Bernd NEBEL; Jiří DAMBORSKÝ a Bernhard HAUER. Engineering CYP153A(M.aq) to Oxyfunctionalize its Inhibitor Dodecylamine Using a LC/MS Based Rapid Flow Analysis Screening. \textit{ChemCatChem}. WEINHEIM: WILEY-V C H VERLAG GMBH, 2022, roč.~14, č.~6, s.~1-5. ISSN~1867-3880. Dostupné z: https://doi.org/10.1002/cctc.202101648.

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