title: Methyl-esterified 3-hydroxybutyrate oligomers protect bacteria from hydroxyl radicals.
abstract: Bacteria rely mainly on enzymes, glutathione and other low-molecular weight thiols to overcome oxidative stress. However, hydroxyl radicals are the most cytotoxic reactive oxygen species, and no known enzymatic system exists for their detoxification. We now show that methyl-esterified dimers and trimers of 3-hydroxybutyrate (ME-3HB), produced by bacteria capable of polyhydroxybutyrate biosynthesis, have 3-fold greater hydroxyl radical-scavenging activity than glutathione and 11-fold higher activity than vitamin C or the monomer 3-hydroxybutyric acid. We found that ME-3HB oligomers protect hypersensitive yeast deletion mutants lacking oxidative stress-response genes from hydroxyl radical stress. Our results show that phaC and phaZ, encoding polymerase and depolymerase, respectively, are activated and polyhydroxybutyrate reserves are degraded for production of ME-3HB oligomers in bacteria infecting plant cells and exposed to hydroxyl radical stress. We found that ME-3HB oligomer production is widespread, especially in bacteria adapted to stressful environments. We discuss how ME-3HB oligomers could provide opportunities for numerous applications in human health.
authors.affiliation: Genetics and Physiology, University of Oulu, Oulu, Finland.
authors.forename: Janne J
authors.identifier: http://orcid.org/0000-0001-8241-3500
authors.initials: JJ
authors.lastname: Koskimäki
authors.affiliation: Department of Chemistry, University of Oulu, Oulu, Finland.|Admescope Ltd., Oulu, Finland.
authors.forename: Marena
authors.initials: M
authors.lastname: Kajula
authors.affiliation: Admescope Ltd., Oulu, Finland.
authors.forename: Juho
authors.initials: J
authors.lastname: Hokkanen
authors.affiliation: Genetics and Physiology, University of Oulu, Oulu, Finland.|Institute of Clinical Microbiology, University of Eastern Finland, Kuopio, Finland.
authors.forename: Emmi-Leena
authors.initials: EL
authors.lastname: Ihantola
authors.affiliation: Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, Agricultural Research Service, Department of Agriculture, Albany, California, USA.
authors.forename: Jong H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Admescope Ltd., Oulu, Finland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Hautajärvi
authors.affiliation: Genetics and Physiology, University of Oulu, Oulu, Finland.
authors.forename: Elina
authors.initials: E
authors.lastname: Hankala
authors.affiliation: Genetics and Physiology, University of Oulu, Oulu, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Suokas
authors.affiliation: Genetics and Physiology, University of Oulu, Oulu, Finland.
authors.forename: Johanna
authors.initials: J
authors.lastname: Pohjanen
authors.affiliation: Institute of Molecular Biology and Genetics of the National Academy of Sciences Ukraine, Kyiv, Ukraine.
authors.forename: Olga
authors.initials: O
authors.lastname: Podolich
authors.affiliation: Institute of Molecular Biology and Genetics of the National Academy of Sciences Ukraine, Kyiv, Ukraine.
authors.forename: Natalia
authors.initials: N
authors.lastname: Kozyrovska
authors.affiliation: Department of Chemistry, University of Oulu, Oulu, Finland.
authors.forename: Ari
authors.initials: A
authors.lastname: Turpeinen
authors.affiliation: Department of Chemistry, University of Oulu, Oulu, Finland.
authors.forename: Mirva
authors.initials: M
authors.lastname: Pääkkönen
authors.affiliation: Department of Chemistry, University of Oulu, Oulu, Finland.
authors.forename: Sampo
authors.initials: S
authors.lastname: Mattila
authors.affiliation: Foodborne Toxin Detection and Prevention Research Unit, Western Regional Research Center, Agricultural Research Service, Department of Agriculture, Albany, California, USA.
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Campbell
authors.affiliation: Genetics and Physiology, University of Oulu, Oulu, Finland.
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Pirttilä
mesh_terms: D000975:Antioxidants / Q000737:chemistry / Q000302:isolation & purification; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D006861:Hydrogen Peroxide; D006885:Hydroxybutyrates / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism / Q000633:toxicity*; D007501:Iron; D020601:Methylobacterium extorquens / Q000378:metabolism*; D015394:Molecular Structure; D028223:Pinus / Q000382:microbiology; D010935:Plant Diseases; D036226:Seedlings
chemical_list: D000975:Antioxidants; D001426:Bacterial Proteins; D006885:Hydroxybutyrates; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D007501:Iron