title: Sequential Enzymatic Conversion of α-Angelica Lactone to γ-Valerolactone through Hydride-Independent C=C Bond Isomerization.
abstract: A case of hydride-independent reaction catalyzed by flavin-dependent ene-reductases from the Old Yellow Enzyme (OYE) family was identified. α-Angelica lactone was isomerized to the conjugated β-isomer in a nicotinamide-free and hydride-independent process. The catalytic cycle of C=C bond isomerization appears to be flavin-independent and to rely solely on a deprotonation-reprotonation sequence through acid-base catalysis. Key residues in the enzyme active site were mutated and provided insight on important mechanistic features. The isomerization of α-angelica lactone by OYE2 in aqueous buffer furnished 6.3 mm β-isomer in 15 min at 30 °C. In presence of nicotinamide adenine dinucleotide (NADH), the latter could be further reduced to γ-valerolactone. This enzymatic tool was successfully applied on semi-preparative scale and constitutes a sustainable process for the valorization of platform chemicals from renewable resources.
authors.affiliation: Department of Chemistry, University of Graz, Heinrichstrasse 28, 8010, Graz, Austria.
authors.forename: Nikolaus G
authors.initials: NG
authors.lastname: Turrini
authors.affiliation: Department of Chemistry, University of Graz, Heinrichstrasse 28, 8010, Graz, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Eger
authors.affiliation: Department of Chemistry, University of Graz, Heinrichstrasse 28, 8010, Graz, Austria.|ACIB GmbH, Department of Chemistry, University of Graz, Heinrichstrasse 28, 8010, Graz, Austria.
authors.forename: Tamara C
authors.initials: TC
authors.lastname: Reiter
authors.affiliation: Department of Chemistry, University of Graz, Heinrichstrasse 28, 8010, Graz, Austria.
authors.forename: Kurt
authors.initials: K
authors.lastname: Faber
authors.affiliation: Department of Chemistry, University of Graz, Heinrichstrasse 28, 8010, Graz, Austria.
authors.forename: Mélanie
authors.identifier: http://orcid.org/0000-0003-4539-1992
authors.initials: M
authors.lastname: Hall
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D020134:Catalytic Domain; D006859:Hydrogen / Q000737:chemistry*; D007536:Isomerism; D007783:Lactones / Q000737:chemistry*; D010088:Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D013696:Temperature
chemical_list: D007783:Lactones; C019257:angelica lactone; D002244:Carbon; D006859:Hydrogen; D010088:Oxidoreductases; C037556:gamma-valerolactone; D015107:4-Butyrolactone
keywords: biobased chemicals; biocatalysis; ene-reductases; isomerization; α-angelica lactone