論文

査読有り 国際誌
2018年5月22日

Microbial production of novel sulphated alkaloids for drug discovery.

Scientific reports
  • Eitaro Matsumura
  • ,
  • Akira Nakagawa
  • ,
  • Yusuke Tomabechi
  • ,
  • Shinichi Ikushiro
  • ,
  • Toshiyuki Sakaki
  • ,
  • Takane Katayama
  • ,
  • Kenji Yamamoto
  • ,
  • Hidehiko Kumagai
  • ,
  • Fumihiko Sato
  • ,
  • Hiromichi Minami

8
1
開始ページ
7980
終了ページ
7980
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41598-018-26306-7

Natural products from plants are useful as lead compounds in drug discovery. Plant benzylisoquinoline alkaloids (BIAs) exhibit various pharmaceutical activities. Although unidentified BIAs are expected to be of medicinal value, sufficient quantities of such BIAs, for biological assays, are sometimes difficult to obtain due to their low content in natural sources. Here, we showed that high productivity of BIAs in engineered Escherichia coli could be exploited for drug discovery. First, we improved upon the previous microbial production system producing (S)-reticuline, an important BIA intermediate, to obtain yields of around 160 mg/L, which was 4-fold higher than those of the previously reported highest production system. Subsequently, we synthesised non-natural BIAs (O-sulphated (S)-reticulines) by introducing human sulphotransferases into the improved (S)-reticuline production system. Analysis of human primary cells treated with these BIAs demonstrated that they affected a biomarker expression in a manner different from that by the parent compound (S)-reticuline, suggesting that simple side-chain modification altered the characteristic traits of BIA. These results indicated that highly productive microbial systems might facilitate the production of scarce or novel BIAs and enable subsequent evaluation of their biological activities. The system developed here could be applied to other rare natural products and might contribute to the drug-discovery process as a next-generation strategy.

リンク情報
DOI
https://doi.org/10.1038/s41598-018-26306-7
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29789647
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964154
ID情報
  • DOI : 10.1038/s41598-018-26306-7
  • PubMed ID : 29789647
  • PubMed Central 記事ID : PMC5964154

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