ABSTRACT
Sesquiterpenoids are one of the most diverse groups in natural compounds with various chemical structures and bioactivities. In our previous work, we developed the chemoenzymatic oxygenation method based on the combination of Fe(II)-EDTA and ferric-chelate reductase that could synthesize (-)-rotundone, a key aroma sesquiterpenoid of black pepper. Fe(II)-EDTA catalyzed the oxygenation of sesquiterpene to sesquiterpenoid, and ferric-chelate reductase catalyzed the supply and regeneration of Fe(II)-EDTA in this system. We then investigated the effect of various Fe2+-chelates on the catalytic oxygenation of sesquiterpene and applied this system to the synthesis of odor sesquiterpenoids. We determined Fe(II)-NTA to be an efficient oxygenation catalyst by the screening approach focusing on ligand structures and coordination atoms of Fe2+-chelates. Valuable odor sesquiterpenoids such as (+)-nootkatone, (-)-isolongifolenone, and (-)-ß-caryophyllene oxide were oxygenatively synthesized from each precursor sesquiterpene by 66%, 82%, and 67% of the molar conversion rate, respectively.Abbreviations: EDTA: ethylenediaminetetraacetate; NTA: nitrilotriacetate; DTPA: diethylenetriaminepentaacetate; phen: o-phenanthroline; cyclam: 1,4,8,11-tetraazacyclotetradecane; TPA: tris(2-pyridylmethyl)amine; GlcDH: glucose dehydrogenase; HP-ß-CD: hydroxypropyl-ß-cyclodextrin.
Subject(s)
FMN Reductase/metabolism , Iron Chelating Agents/chemistry , Oxygen/metabolism , Sesquiterpenes/chemical synthesis , Catalysis , Cyclodextrins/metabolism , Glucose 1-Dehydrogenase/metabolism , LigandsABSTRACT
(-)-Rotundone, a sesquiterpenoid that has a characteristic woody and peppery odor, is a key aroma component of spicy foodstuffs, such as black pepper and Australian Shiraz wine. (-)-Rotundone shows the lowest level of odor threshold in natural compounds and remarkably improves the quality of various fruit flavors. To develop a method for the synthesis of (-)-rotundone, we focused on non-heme Fe2+-chelates, which are biomimetic catalysts of the active center of oxygenases and enzymatic supply and regeneration of those catalysts. That is, we constructed a unique combination system composed of the oxidative synthesis of (-)-rotundone using the non-heme Fe2+-chelate catalyst, Fe(II)-EDTA, and the enzymatic supply and regeneration of Fe2+-chelate by ferric-chelate reductase, YqjH, from Escherichia coli. In addition, we improved the yield of (-)-rotundone by the application of cyclodextrin and glucose dehydrogenase to this system, and thus established a platform for efficient (-)-rotundone production.