title: Natural low-molecular mass organic compounds with oxidase activity as organocatalysts.
abstract: Organocatalysts, low-molecular mass organic compounds composed of nonmetallic elements, are often used in organic synthesis, but there have been no reports of organocatalysts of biological origin that function in vivo. Here, we report that actinorhodin (ACT), a natural product derived from Streptomyces coelicolor A3(2), acts as a biocatalyst. We purified ACT and assayed its catalytic activity in the oxidation of L-ascorbic acid and L-cysteine as substrates by analytical methods for enzymes. Our findings were as follows: (i) oxidation reactions producing H2O2 proceeded upon addition of ACT to the reaction mixture; (ii) ACT was not consumed during the reactions; and (iii) a small amount (catalytic amount) of ACT consumed an excess amount of the substrates. Even at room temperature, atmospheric pressure, and neutral pH, ACT showed catalytic activity in aqueous solution, and ACT exhibited substrate specificity in the oxidation reactions. These findings reveal ACT to be an organocatalyst. ACT is known to show antibiotic activity, but its mechanism of action remains unknown. On the basis of our results, we propose that ACT kills bacteria by catalyzing the production of toxic levels of H2O2. We also screened various other natural products of bacterial, plant, and animal origins and found that several of the compounds exhibited catalytic activity, suggesting that living organisms produce and use these compounds as biocatalysts in nature.
authors.affiliation: Institute of Applied Biochemistry and Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan; and.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Nishiyama
authors.affiliation: Institute of Applied Biochemistry and Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan; and.
authors.forename: Yoshiteru
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Enzyme-Sensor Co., Ltd., 2-1-6 Sengen, Tsukuba, Ibaraki 305-0047, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kusakabe
authors.affiliation: Institute of Applied Biochemistry and Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan; and.
authors.forename: Takuto
authors.initials: T
authors.lastname: Kumano
authors.affiliation: Institute of Applied Biochemistry and Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8572, Japan; and.
authors.forename: Michihiko
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000880:Anthraquinones / Q000737:chemistry / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism; D001205:Ascorbic Acid / Q000378:metabolism; D001688:Biological Products / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D015394:Molecular Structure; D008970:Molecular Weight; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D048372:Streptomyces coelicolor / Q000378:metabolism*; D013379:Substrate Specificity; D013696:Temperature; D000095622:Benzoisochromanequinones
chemical_list: D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D001205:Ascorbic Acid; D001688:Biological Products; D003545:Cysteine; D006861:Hydrogen Peroxide; D010088:Oxidoreductases; C013390:actinorhodin; D000095622:Benzoisochromanequinones
keywords: actinorhodin; antibiotics; catalysis; oxidation