Abstract
BackgroundPterostilbene, 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.ResultsWe 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.ConclusionAs 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.
Highlights
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
This p-coumaroyl-CoA is condensed with three molecules of malonyl-CoA via stilbene synthase (STS), which is the key enzyme in resveratrol synthesis
Schmidlin et al [8] first reported that resveratrol O-methyltransferase (ROMT), which is induced by fungal infection in grapevine leaves, could catalyze the direct conversion of resveratrol into pterostilbene
Summary
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. Heo et al Microb Cell Fact (2017) 16:30 higher biological activity of pterostilbene over its parental compound resveratrol [3, 7]. In this pathway, tyrosine is converted into p-coumaric acid using tyrosine ammonia lyase (TAL). The p-coumaric acid is activated to p-coumaroyl-CoA with the p-coumarate CoA ligase (CCL) This p-coumaroyl-CoA is condensed with three molecules of malonyl-CoA via stilbene synthase (STS), which is the key enzyme in resveratrol synthesis. Resveratrol is converted into its methylated analogs, pinostilbene and pterostilbene, through resveratrol O-methyltransferase (ROMT). Only a few plant ROMT genes have been isolated and characterized [8,9,10,11]
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