Structure-Guided Redesign of CYP153AM.aq for the Improved Terminal Hydroxylation of Fatty Acids

Sara Hoffmann; Hamid-Reza Danesh-Azari; Claudia Spandolf; Martin  Weissenborn; Gideon James Grogan; Bernhard Hauer

doi:10.1002/cctc.201600680

Structure-Guided Redesign of CYP153AM.aq for the Improved Terminal Hydroxylation of Fatty Acids

Sara Hoffmann, Hamid-Reza Danesh-Azari, Claudia Spandolf, Martin Weissenborn, Gideon James Grogan, Bernhard Hauer

Chemistry

Research output: Contribution to journal › Article › peer-review

Abstract

The structure of a P450 ω-hydroxylase bound to its fatty acid product was determined, which revealed a narrow substrate tunnel that leads to the heme. The introduction of an arginine side chain in proximity to the carboxyl group of the fatty acid led to a reduced KM value for dodecanoic acid, which suggests the importance of an anchoring point in the active site. An increase in the flexibility of the substrate recognition region was also engineered, which resulted in a threefold improved product formation.

Original language	English
Pages (from-to)	3234–3239
Number of pages	6
Journal	ChemCatChem
Volume	8
Issue number	20
DOIs	https://doi.org/10.1002/cctc.201600680
Publication status	E-pub ahead of print - 6 Sept 2016

Bibliographical note

© 2016, Wiley-VCH Verlag GmbH & Co. K. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.

Access to Document

10.1002/cctc.201600680

Accepted Manuscript
© 2016, Wiley-VCH Verlag GmbH & Co. K. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details.
Accepted author manuscript, 2.09 MB

Cite this

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abstract = "The structure of a P450 ω-hydroxylase bound to its fatty acid product was determined, which revealed a narrow substrate tunnel that leads to the heme. The introduction of an arginine side chain in proximity to the carboxyl group of the fatty acid led to a reduced KM value for dodecanoic acid, which suggests the importance of an anchoring point in the active site. An increase in the flexibility of the substrate recognition region was also engineered, which resulted in a threefold improved product formation.",

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AU - Weissenborn, Martin

AU - Grogan, Gideon James

AU - Hauer, Bernhard

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