title: Metabolic engineering of Saccharomyces cerevisiae producing nicotianamine: potential for industrial biosynthesis of a novel antihypertensive substrate.
abstract: 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 microg/g wet weight. Successful production of NA in S. cerevisiae should pave the way for industrial production of this novel antihypertensive substrate.
authors.affiliation: Graduate School of Agricultural and Life Sciences, The University of Tokyo.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Wada
authors.forename: Takanori
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Michiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nakanishi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mori
authors.forename: Naoko K
authors.initials: NK
authors.lastname: Nishizawa
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism; D000959:Antihypertensive Agents / Q000737:chemistry / Q000378:metabolism*; D001383:Azetidinecarboxylic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D049109:Cell Proliferation; D003470:Culture Media; D004345:Drug Industry; D018628:Gene Dosage / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D005822:Genetic Vectors / Q000235:genetics; D015394:Molecular Structure; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000959:Antihypertensive Agents; D003470:Culture Media; D011994:Recombinant Proteins; C082893:nicotianamine; D001383:Azetidinecarboxylic Acid; D019883:Alkyl and Aryl Transferases; C118230:nicotianamine synthase