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Precursor‐directed biosynthesis of stilbene methyl ethers in Escherichia coli
Author(s) -
Katsuyama Yohei,
Fuobutaka,
Horinouchi Sueharu
Publication year - 2007
Publication title -
biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.144
H-Index - 84
eISSN - 1860-7314
pISSN - 1860-6768
DOI - 10.1002/biot.200700098
Subject(s) - escherichia coli , biochemistry , chemistry , biosynthesis , phenylalanine ammonia lyase , phenylalanine , coenzyme a , metabolic engineering , prenyltransferase , reductase , enzyme , gene , amino acid
Stilbenes are bioactive compounds that show beneficial effects for humans, such as anti‐tumor activity and survival improvement. Resveratrol, a representative of stilbenes and showing various health‐improving activities, is rapidly metabolized in humans, and modified resveratrols are therefore desired as anti‐cancer drugs and dietary polyphenols. An Escherichia coli system, in which an artificial stilbene biosynthetic pathway, including steps of phenylalanine ammonia‐lyase, 4‐coumarate:CoA ligase, and stilbene synthase, was reconstructed, produced stilbenes in high yields: resveratrol from tyrosine and pinosylvin from phenylalanine. To incorporate a stilbene methyltransferase gene into this E. coli system, cDNA of Os08g06100 in Oryza sativa was expressed and its O ‐methylating activity toward stilbenes was confirmed. Incorporation of the pinosylvin methyltransferase (OsPMT) gene into the pathway established in E. coli led to production of mono‐ and di‐methylated stilbenes. Furthermore, the OsPMT gene turned out to be useful in production of unnatural stilbene methyl ethers due to its rather relaxed substrate specificity; various carboxylic acids supplemented as precursors, such as p ‐fluorocinnamic acid, 3‐(2‐furyl)acrylic acid, 3‐(2‐thienyl)acrylic acid, and 3‐(3‐pyridyl)acrylic acid, to the E. coli system carrying the steps of 4‐coumarate:CoA ligase, stilbene synthase, and OsPMT were converted to stilbene dimethyl ethers with the corresponding carboxylic moiety.