Metabolic Engineering of<i>Saccharomyces cerevisiae</i>Producing Nicotianamine: Potential for Industrial Biosynthesis of a Novel Antihypertensive Substrate

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  • WADA Yasuaki
    Graduate School of Agricultural and Life Sciences, The University of Tokyo
  • KOBAYASHI Takanori
    Graduate School of Agricultural and Life Sciences, The University of Tokyo Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST)
  • TAKAHASHI Michiko
    Graduate School of Agricultural and Life Sciences, The University of Tokyo
  • NAKANISHI Hiromi
    Graduate School of Agricultural and Life Sciences, The University of Tokyo
  • MORI Satoshi
    Graduate School of Agricultural and Life Sciences, The University of Tokyo
  • NISHIZAWA Naoko K.
    Graduate School of Agricultural and Life Sciences, The University of Tokyo Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST)

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  • Metabolic Engineering of Saccharomyces cerevisiae Producing Nicotianamine: Potential for Industrial Biosynthesis of a Novel Antihypertensive Substrate

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Nicotianamine (NA), a metal chelator, is ubiquitous in higher plants. In humans, NA inhibits angiotensin I-converting enzyme (ACE), and consequently reduces high blood pressure. Nicotianamine is synthesized from the trimerization of S-adenosylmethionine (SAM) by NA synthase (NAS). Here, we aimed to produce large amounts of NA fermentatively by introducing the Arabidopsis AtNAS2 gene into Saccharomyces cerevisiae strain SCY4. This strain can accumulate up to 100 times the usual amount of SAM, and this is considered desirable for overproduction of NA. Nicotianamine was produced in the engineered yeast, and the NA level increased with incubation time until the stationary phase. The maximum concentration of intracellular NA obtained was 766±33 μg/g wet weight. Successful production of NA in S. cerevisiae should pave the way for industrial production of this novel antihypertensive substrate.

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