|Koskimaki, Janne - University Of Oulu|
|Kajula, Marena - University Of Oulu|
|Hokkanen, Juho - Admescope Ltd|
|Ihantola, Emmi-leena - University Of Oulu|
|Kim, Jong - Former ARS Employee|
|Hautajarvi, Heidi - Admescope Ltd|
|Hankala, Elina - University Of Oulu|
|Suokas, Marko - University Of Oulu|
|Pohjanen, Johanna - University Of Oulu|
|Podolich, Olga - National Scientific Center|
|Kozyrovska, Natalia - National Scientific Center|
|Turpeinen, Ari - University Of Oulu|
|Paakkonen, Mirva - University Of Oulu|
|Mattila, Sampo - University Of Oulu|
|Campbell, Bruce - Former ARS Employee|
|Pirttila, Anna Maria - University Of Oulu|
|Cheng, Luisa Wai Wai|
Submitted to: Nature Chemical Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/5/2016
Publication Date: 3/14/2016
Citation: Koskimaki, J.J., Kajula, M., Hokkanen, J., Ihantola, E., Kim, J.H., Hautajarvi, H., Hankala, E., Suokas, M., Pohjanen, J., Podolich, O., Kozyrovska, N., Turpeinen, A., Paakkonen, M., Mattila, S., Campbell, B.C., Pirttila, A., Cheng, L.W. 2016. Methyl-esterified 3-hydroxybutyrate oligomers protect bacteria from hydroxyl radicals. Nature Chemical Biology. 2016 12:332-338. doi: 10.1038/nchembio.2043.
Interpretive Summary: Resistance to oxidative stress is particularly important during the process of infection, where targeted hydroxyl radical production by the host is activated. In plants, localized release of iron from cell wall appositions, simultaneously with systemic distribution of reactive oxygen species during the oxidative burst, results in targeted production of hydroxyl radicals at the sites of microbial penetration of host cells. Results show that products of poly-3-hydroxybutyric acid depolymerization, methyl-esterified oligomers of 3-hydroxybutyrate, have antioxidative activity three-times greater than glutathione, the main known detoxifier of hydroxyl radicals in bacterial cell. Results further demonstrate that production of these oligomers is activated in response to hydroxyl-radical stress.
Technical 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.