(R,S)-Tetrahydropapaveroline production by stepwise fermentation using engineered Escherichia coli

• Nakagawa, Akira

• Matsuzaki, Chiaki

• Matsumura, Eitaro

• Koyanagi, Takashi

• Katayama, Takane

• Yamamoto, Kenji

• Sato, Fumihiko

• Kumagai, Hidehiko

• Minami, Hiromichi

Abstract

Tetrahydropapaveroline (THP), a benzylisoquinoline alkaloid (BIA) found in diverse pharmaceutical compounds, is used as a starting material for the production of BIA. THP also has various neurobiological properties but is difficult to synthesize. Therefore, a simple method for THP production is desired. Recent studies have shown that microbes, especially bacteria, can serve as platforms for synthesizing these complex compounds; however, because bacteria lack organelles, the designed synthetic pathway cannot be compartmentalized. Thus, the metabolic flow is frequently inhibited or disrupted by undesirable reactions. Indeed, in the first attempt to synthesize THP using a single strain of engineered Escherichia coli, the yield was quite low (<5 μM), mainly because of the oxidation of THP by tyrosinase, an essential enzyme in our production system. To circumvent these problems, we constructed a stepwise (R, S)-THP production system, in which the dopamine-producing step and the subsequent THP-producing step were separated. The yield of (R, S)-THP reached 1.0 mM (287 mg/L), the highest yielding BIA production method using a microbe reported to date. Furthermore, we demonstrated that (R, S)-THP produced by stepwise fermentation is useful for the production of reticuline, an important BIAs intermediate. Based on these observations, applying the stepwise fermentation method is discussed.

Journal

• Scientific Reports

  Scientific Reports 4 2017-10-21

  Springer Nature

Keywords

• Biotechnology
• Industrial microbiology
• Microbiology

Details

• CRID: 1050001335851890304
• NII Article ID: 120006358778
• ISSN: 20452322
• HANDLE: 2433/227723
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles