title: Biosynthesis of methylated resveratrol analogs through the construction of an artificial biosynthetic pathway in E. coli.
abstract: BACKGROUND
  Methylated resveratrol analogs show similar biological activities that are comparable with those of the resveratrol. However, the methylated resveratrol analogs exhibit better bioavailability as they are more easily transported into the cell and more resistant to degradation. Although these compounds are widely used in human health care and in industrial materials, at present they are mainly obtained by extraction from raw plant sources. Accordingly their production can suffer from a variety of economic problems, including low levels of productivity and/or heterogeneous quality. On this backdrop, large-scale production of plant metabolites via microbial approaches is a promising alternative to chemical synthesis and extraction from plant sources.
  
  
  RESULTS
  An Escherichia coli system containing an artificial biosynthetic pathway that produces methylated resveratrol analogues, such as pinostilbene (3,4'-dihydroxy-5-methoxystilbene), 3,5-dihydroxy-4'-methoxystilbene, 3,4'-dimethoxy-5-hydroxystilbene, and 3,5,4'-trimethoxystilbene, from simple carbon sources is developed. These artificial biosynthetic pathways contain a series of codon-optimized O-methyltransferase genes from sorghum in addition to the resveratrol biosynthetic genes. The E. coli cells that harbor pET-opTLO1S or pET-opTLO3S produce the one-methyl resveratrol analogues of 3,5-dihydroxy-4'-methoxystilbene and pinostilbene, respectively. Furthermore, the E. coli cells that harbor pET-opTLO13S produce 3,5-dihydroxy-4'-methoxystilbene, bis-methyl resveratrol (3,4'-dimethoxy-5-hydroxystilbene), and tri-methyl resveratrol (3,5,4'-trimethoxystilbene).
  
  
  CONCLUSIONS
  Our strategy demonstrates the first harness microorganisms for de novo synthesis of methylated resveratrol analogs used a single vector system joined with resveratrol biosynthetic genes and sorghum two resveratrol O-methyltransferase genes. Thus, this is also the first report on the production of the methylated resveratrol compounds bis-methyl and tri-methyl resveratrol (3,4'-dimethoxy-5-hydroxystilbene and 3,5,4'-trimethoxystilbene) in the E. coli culture. Thus, the production of the methylated resveratrol compounds was performed on the simple E. coli medium without precursor feeding in the culture.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kang
authors.forename: Jae Kyoung
authors.initials: JK
authors.lastname: Lee
authors.forename: Oksik
authors.initials: O
authors.lastname: Choi
authors.forename: Cha Young
authors.initials: CY
authors.lastname: Kim
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Jang
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.affiliation: Chemical Biology Research Center, Korea Research Institute of Bioscience and Biotechnology(KRIBB), 30 Yeongudanji-ro, Ochang-eup, Chungbuk 363-883, Republic of Korea. hongsoo@kribb.re.kr.
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Hong
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004926:Escherichia coli / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D013058:Mass Spectrometry; D008745:Methylation; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D045868:Sorghum / Q000201:enzymology; D013267:Stilbenes / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*
chemical_list: C439024:3,5-dihydroxy-4'-methoxystilbene; D010940:Plant Proteins; D013267:Stilbenes; C522997:pinostilbene; D008780:Methyltransferases; D000077185:Resveratrol