De novo biosynthesis of pterostilbene in an Escherichia coli strain using a new resveratrol O-methyltransferase from Arabidopsis

Microb Cell Fact. 2017 Feb 15;16(1):30. doi: 10.1186/s12934-017-0644-6.


Background: Pterostilbene, a structural analog of resveratrol, has higher oral bioavailability and bioactivity than that of the parent compound; but is far less abundant in natural sources. Thus, to efficiently obtain this bioactive resveratrol analog, it is necessary to develop new bioproduction systems.

Results: We identified a resveratrol O-methyltransferase (ROMT) function from a multifunctional caffeic acid O-methyltransferase (COMT) originating from Arabidopsis, which catalyzes the transfer of a methyl group to resveratrol resulting in pterostilbene production. In addition, we constructed a biological platform to produce pterostilbene with this ROMT gene. Pterostilbene can be synthesized from intracellular L-tyrosine, which requires the activities of four enzymes: tyrosine ammonia lyase (TAL), p-coumarate:CoA ligase (CCL), stilbene synthase (STS) and resveratrol O-methyltransferase (ROMT). For the efficient production of pterostilbene in E. coli, we used an engineered E. coli strain to increase the intracellular pool of L-tyrosine, which is the initial precursor of pterostilbene. Next, we tried to produce pterostilbene in the engineered E. coli strain using L-methionine containing media, which is used to increase the intracellular pool of S-adenosyl-L-methionine (SAM). According to this result, pterostilbene production as high as 33.6 ± 4.1 mg/L was achieved, which was about 3.6-fold higher compared with that in the parental E. coli strain harboring a plasmid for pterostilbene biosynthesis.

Conclusion: As a potential phytonutrient, pterostilbene was successfully produced in E. coli from a glucose medium using a single vector system, and its production titer was also significantly increased using a L-methionine containing medium in combination with a strain that had an engineered metabolic pathway for L-tyrosine. Additionally, we provide insights into the dual functions of COMT from A. thaliana which was characterized as a ROMT enzyme.

Keywords: De novo biosynthesis; Pterostilbene; Resveratrol O-methyltransferase.

MeSH terms

  • Acyltransferases / metabolism
  • Ammonia-Lyases / metabolism
  • Arabidopsis / enzymology*
  • Biocatalysis
  • Escherichia coli / drug effects
  • Escherichia coli / enzymology
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Metabolic Engineering / methods*
  • Metabolic Networks and Pathways
  • Methionine / pharmacology
  • Methyltransferases / genetics*
  • Methyltransferases / metabolism*
  • Resveratrol
  • S-Adenosylmethionine / metabolism
  • Stilbenes / chemistry
  • Stilbenes / metabolism*
  • Tyrosine / metabolism


  • Stilbenes
  • pterostilbene
  • Tyrosine
  • S-Adenosylmethionine
  • Methionine
  • Methyltransferases
  • caffeate O-methyltransferase
  • Acyltransferases
  • stilbene synthase
  • Ammonia-Lyases
  • L-tyrosine ammonia-lyase
  • Resveratrol