title: Squalene hopene cyclases are protonases for stereoselective Brønsted acid catalysis.
abstract: For many important reactions catalyzed in chemical laboratories, the corresponding enzymes are missing, representing a restriction in biocatalysis. Although nature provides highly developed machineries appropriate to catalyze such reactions, their potential is often ignored. This also applies to Brønsted acid catalysis, a powerful method to promote a myriad of chemical transformations. Here, we report on the unique protonation machinery of a squalene hopene cyclase (SHC). Active site engineering of this highly evolvable enzyme yielded a platform for enzymatic Brønsted acid catalysis in water. This is illustrated by activation of different functional groups (alkenes, epoxides and carbonyls), enabling the highly stereoselective syntheses of various cyclohexanoids while uncoupling SHC from polycyclization chemistry. This work highlights the potential of systematic investigation on nature's catalytic machineries to generate unique catalysts.
authors.affiliation: Institute of Technical Biochemistry, University of Stuttgart, Stuttgart, Germany.
authors.forename: Stephan C
authors.identifier: 0000000236209362
authors.initials: SC
authors.lastname: Hammer
authors.affiliation: Institute of Technical Biochemistry, University of Stuttgart, Stuttgart, Germany.
authors.forename: Antonija
authors.initials: A
authors.lastname: Marjanovic
authors.affiliation: Institute of Technical Biochemistry, University of Stuttgart, Stuttgart, Germany.
authors.forename: Jörg M
authors.initials: JM
authors.lastname: Dominicus
authors.affiliation: Institute of Technical Biochemistry, University of Stuttgart, Stuttgart, Germany.
authors.forename: Bettina M
authors.initials: BM
authors.lastname: Nestl
authors.affiliation: Institute of Technical Biochemistry, University of Stuttgart, Stuttgart, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Hauer
mesh_terms: D000080462:Acyclic Monoterpenes; D000447:Aldehydes / Q000737:chemistry; D001665:Binding Sites; D055162:Biocatalysis; D003500:Cyclization; D057927:Hydrophobic and Hydrophilic Interactions; D019751:Intramolecular Transferases / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D015394:Molecular Structure; D039821:Monoterpenes / Q000737:chemistry; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D015202:Protein Engineering; D011522:Protons; D013185:Squalene / Q000737:chemistry; D013237:Stereoisomerism; D013379:Substrate Specificity; D014315:Triterpenes / Q000737:chemistry
chemical_list: D000080462:Acyclic Monoterpenes; D000447:Aldehydes; D039821:Monoterpenes; D011522:Protons; D014315:Triterpenes; C028765:diploptene; D013185:Squalene; D019751:Intramolecular Transferases; C066630:squalene-hopene cyclase; C108217:citronellal