Cytochrome P450 mediated hydroxylation of ibuprofen using Pichia pastoris as biocatalyst. (January 2019)

• Record Type: Journal Article
• Authors: Rinnofner, Claudia; Kerschbaumer, Bianca; Weber, Hansjörg; Glieder, Anton; Winkler, Margit
• Is Part Of: Biocatalysis and agricultural biotechnology. Number 17(2019)
• Page Start: 525
• Page End: 528
• Publication Date: 2019-01
• Subjects: Cytochrome P450 -- Ibuprofen -- Hydroxylation -- API Metabolism; Agricultural biotechnology -- Periodicals; Enzymes -- Biotechnology -- Periodicals; 660.6
• DOI: 10.1016/j.bcab.2018.12.022
• Languages: English
• ISSNs: 1878-8181

Abstract

Abstract: Class VIII self-sufficient CYP from Aspergillus fumigatus (CYP505X) and a variant with five mutations were heterologously expressed in Pichia pastoris. Ibuprofen – a widely used non-steroidal anti-inflammatory drug (NSAID) – was oxidized most efficiently in a whole cell mediated biotransformation. The two major metabolites were isolated by preparative HPLC and their structure elucidated by NMR. Specifically, ibuprofen was hydroxylated at the tertiary carbon atom and the benzylic position on the lipophilic side chain. Highlights: Microbial system established for the preparation of 1-hydroxyibuprofen and 2-hydroxyibuprofen. Pichia pastoris expresses soluble CYP. 13 APIs oxidized by microbial CYP in form of P. pastoris whole cell biocatalyst. Activity of CYP505 quintuple mutant superior to the respective wild-type and selectivities different.