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Accessing the Biocatalytic Potential for C−H‐Activation by Targeted Genome Mining and Screening
Author(s) -
Schmitz Lisa Marie,
Schäper Jonas,
Rosenthal Katrin,
Lütz Stephan
Publication year - 2019
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.201901273
Subject(s) - biotransformation , monooxygenase , chemistry , biocatalysis , drug discovery , biochemical engineering , substrate (aquarium) , biomolecule , cytochrome p450 , combinatorial chemistry , computational biology , biochemistry , catalysis , biology , enzyme , reaction mechanism , engineering , ecology
Abstract Cytochrome P450 monooxygenases (P450s) are ubiquitous hemeproteins that insert oxygen specifically into substrates leading to diverse chemical transformations. Utilizing their capabilities, microbial whole‐cell biocatalysts are applied in pharmaceutical and fine chemical industry to produce biomolecules and drug metabolites. In order to synthesize novel bioactive compounds there is a great demand to identify P450s with new reaction and substrate scope. In this study, genome mining and an activity screening were successfully combined to discover so far underutilized biocatalysts. The screening revealed the expected broad range of reactions, such as hydroxylations, dealkylations, reductions and desaturations. For Actinosynnema mirum and ritonavir the biotransformation was transferred to a preparative scale resulting in a ritonavir conversion of 90 % after 48 h and 13 different metabolites analyzed by LC‐MS 2 and NMR. These results clearly demonstrate the potential of the underlying approach to identify promising whole cell biocatalysts with good conversion and product scopes.