Rational Biocatalyst Design for a Cyanide-Free Synthesis of Long-Chain Fatty Nitriles from Their Aldoximes

Yavuzer H, Yang J, Gröger H (2023)
European Journal of Lipid Science and Technology 125(5): 2200177.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
Download
OA 1.21 MB
Abstract / Bemerkung
Recently, the capability of the aldoxime dehydratase from Bacillus sp. (OxdB) for the transformation of fatty aldoximes into fatty nitriles with impressive substrate loadings is reported. However, the substrate scope of this biocatalyst turned out to be limited in terms of the chain length with decanal oxime being the substrate with the longest well tolerated n-alkyl chain. Besides the increased bulkiness of the long-chain aldoximes, their strongly decreased water solubility represents a further hurdle for an efficient biotransformation. Addressing this challenge of an expanded substrate spectrum comprising long-chain fatty aldoximes, this work investigates the substrate solubility and enzyme kinetics in combination with molecular modeling in order to find an enzyme mutant being suitable for C12- to C16-aldoximes. Both, fatty aldoxime solubility in water and the active site of the wild-type enzyme OxdB are identified as critical issues for an efficient biotransformation of these substrates. The activity issue is addressed by a rational design of a mutant using a homology modeling as well as a molecular modeling software suitable for enzymes. With the resulting double mutant OxdB-F289A/L293A, this report can achieve successful biotransformations with the C12- to C16-aldoximes at substrate concentrations of 250 x 10(-3) to 1000 x 10(-3) m. For example, an excellent conversion of >99% is obtained with tetradecanal oxime.Practical applications: Fatty nitriles with a prolonged chain length of C12 or more are of high interest in industry due to their use for the production of fatty amines on large technical scale. As an alternative route, fatty nitriles can be generated from their aldoximes by means of an aldoxime dehydratase (Oxd) as biocatalyst. The conversion of long-chain fatty aldoximes, however, remained a challenge up to now. This work describes the optimization of the aldoxime dehydratase OxdB from Bacillus sp. for the dehydration of nonsoluble bulky fatty aldoximes. The created variant can convert long chain fatty aldoximes toward the corresponding nitrile as demonstrated for C12- to C16-nitriles. In addition, high conversion (of up to >99%) is achieved when operating at high substrate concentrations of up to 1000 x 10(-3) m, thus making this approach interesting for industrial applications.
Stichworte
aldoxime dehydratase; biocatalysis; fatty aldoximes; fatty nitriles; protein engineering
Erscheinungsjahr
2023
Zeitschriftentitel
European Journal of Lipid Science and Technology
Band
125
Ausgabe
5
Art.-Nr.
2200177
ISSN
1438-7697
eISSN
1438-9312
Finanzierungs-Informationen
Open-Access-Publikationskosten wurden durch die Universität Bielefeld im Rahmen des DEAL-Vertrags gefördert.
Page URI
https://pub.uni-bielefeld.de/record/2979715

Zitieren

Yavuzer H, Yang J, Gröger H. Rational Biocatalyst Design for a Cyanide-Free Synthesis of Long-Chain Fatty Nitriles from Their Aldoximes. European Journal of Lipid Science and Technology . 2023;125(5): 2200177.
Yavuzer, H., Yang, J., & Gröger, H. (2023). Rational Biocatalyst Design for a Cyanide-Free Synthesis of Long-Chain Fatty Nitriles from Their Aldoximes. European Journal of Lipid Science and Technology , 125(5), 2200177. https://doi.org/10.1002/ejlt.202200177
Yavuzer, Hilmi, Yang, Jianing, and Gröger, Harald. 2023. “Rational Biocatalyst Design for a Cyanide-Free Synthesis of Long-Chain Fatty Nitriles from Their Aldoximes”. European Journal of Lipid Science and Technology 125 (5): 2200177.
Yavuzer, H., Yang, J., and Gröger, H. (2023). Rational Biocatalyst Design for a Cyanide-Free Synthesis of Long-Chain Fatty Nitriles from Their Aldoximes. European Journal of Lipid Science and Technology 125:2200177.
Yavuzer, H., Yang, J., & Gröger, H., 2023. Rational Biocatalyst Design for a Cyanide-Free Synthesis of Long-Chain Fatty Nitriles from Their Aldoximes. European Journal of Lipid Science and Technology , 125(5): 2200177.
H. Yavuzer, J. Yang, and H. Gröger, “Rational Biocatalyst Design for a Cyanide-Free Synthesis of Long-Chain Fatty Nitriles from Their Aldoximes”, European Journal of Lipid Science and Technology , vol. 125, 2023, : 2200177.
Yavuzer, H., Yang, J., Gröger, H.: Rational Biocatalyst Design for a Cyanide-Free Synthesis of Long-Chain Fatty Nitriles from Their Aldoximes. European Journal of Lipid Science and Technology . 125, : 2200177 (2023).
Yavuzer, Hilmi, Yang, Jianing, and Gröger, Harald. “Rational Biocatalyst Design for a Cyanide-Free Synthesis of Long-Chain Fatty Nitriles from Their Aldoximes”. European Journal of Lipid Science and Technology 125.5 (2023): 2200177.
Alle Dateien verfügbar unter der/den folgenden Lizenz(en):
Creative Commons Namensnennung 4.0 International Public License (CC-BY 4.0):
Volltext(e)
Access Level
OA Open Access
Zuletzt Hochgeladen
2024-02-13T14:14:38Z
MD5 Prüfsumme
fb64fdc05fd7099793e49c39db6ed172


Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®
Suchen in

Google Scholar