論文

査読有り 筆頭著者 国際誌
2020年7月2日

Pyruvate metabolism redirection for biological production of commodity chemicals in aerobic fungus Aspergillus oryzae.

Metabolic engineering
  • Silai Zhang
  • ,
  • Satoshi Wakai
  • ,
  • Naoya Sasakura
  • ,
  • Hiroko Tsutsumi
  • ,
  • Yoji Hata
  • ,
  • Chiaki Ogino
  • ,
  • Akihiko Kondo

記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.ymben.2020.06.010

Pyruvate is a central metabolite for the biological production of various chemicals. In eukaryotes, pyruvate produced by glycolysis is used in conversion to ethanol and lactate and in anabolic metabolism in the cytosol, or is transported into the mitochondria for use as a substrate in the tricarboxylic acid (TCA) cycle. In this study, we focused on controlling pyruvate metabolism in aerobic microorganisms for the biological production of various chemicals. We successfully improved productivity by redirecting pyruvate metabolism in the aerobic filamentous fungus Aspergillus oryzae via the deletion of two genes that encode pyruvate decarboxylase and mitochondrial pyruvate carriers. Production of ethanol as a major byproduct was completely inhibited, and the limited translocation of pyruvate into the mitochondria shifted the metabolism from respiration for energy conversion to the effective production of lactate or 2,3-butandiole, even under aerobic conditions. Metabolomic and transcriptomic analyses showed an emphasis on glycolysis and a repressed TCA cycle. Although the dry mycelial weights of the deletion mutants were reduced compared with those of wild type, the titer and yields of the target products were drastically increased. In particular, the redirection of pyruvate metabolism shifted from anabolism for biomass production to catabolism for the production of target chemicals. Conclusively, our results indicate that the redirection of pyruvate metabolism is a useful strategy in the metabolic engineering of aerobic microorganisms.

リンク情報
DOI
https://doi.org/10.1016/j.ymben.2020.06.010
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32623009
ID情報
  • DOI : 10.1016/j.ymben.2020.06.010
  • PubMed ID : 32623009

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