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.

Basic information

Original name

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

Authors

RAPP, Lea R., Sérgio Manuel MARQUES (620 Portugal, belonging to the institution), Bernd NEBEL, Jiří DAMBORSKÝ (203 Czech Republic, guarantor, belonging to the institution) and Bernhard HAUER

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10403 Physical chemistry

Country of publisher

Germany

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.500

RIV identification code

RIV/00216224:14310/22:00126696

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1002/cctc.202101648

UT WoS

000749672700001

Keywords in English

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

Abstract

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.

Links

EF17_043/0009632, research and development project

Name: CETOCOEN Excellence

LM2018121, research and development project

Name: Výzkumná infrastruktura RECETOX (Acronym: RECETOX RI)

Investor: Ministry of Education, Youth and Sports of the CR, RECETOX RI

LM2018140, research and development project

Name: e-Infrastruktura CZ (Acronym: e-INFRA CZ)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

RAPP, Lea R., Sérgio Manuel MARQUES, Bernd NEBEL, Jiří DAMBORSKÝ and 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, vol. 14, No 6, p. 1-5. ISSN 1867-3880. Available from: https://dx.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 = {http://dx.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 and 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, vol.~14, No~6, p.~1-5. ISSN~1867-3880. Available from: https://dx.doi.org/10.1002/cctc.202101648.

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