文章基本信息

标题：(R,S)-Tetrahydropapaveroline production by stepwise fermentation using engineered Escherichia coli
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作者：Akira Nakagawa ; Chiaki Matsuzaki ; Eitaro Matsumura 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2015
卷号：4
期号：1
DOI：10.1038/srep06695
语种：English
出版社：Springer Nature
摘要：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 ( 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.