2016
DOI: 10.1016/j.ymben.2016.08.003
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Engineering a microbial platform for de novo biosynthesis of diverse methylxanthines

Abstract: Engineered microbial biosynthesis of plant natural products can support manufacturing of complex bioactive molecules and enable discovery of non-naturally occurring derivatives. Purine alkaloids, including caffeine (coffee), theophylline (antiasthma drug), theobromine (chocolate), and other methylxanthines, play a significant role in pharmacology and food chemistry. Here, we engineered the eukaryotic microbial host Saccharomyces cerevisiae for the de novo biosynthesis of methylxanthines. We constructed a xanth… Show more

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Cited by 36 publications
(28 citation statements)
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“…3-Methylxanthine and other xanthine derivatives have been shown various biomedical effects as adenosine antagonist and inhibitors of Primary Amine Oxidase [57,58]. Besides chemical synthesis, biotransformation and biosynthesis offered alternative way to produce 3-methylxanthine and other xanthine derivatives [22,48]. Due to theophylline degradation characteristic, A. ustus and A. tamarii would be applied in the production of 3-methylxanthine and xanthine with theophylline as feedstock through microbial conversion.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…3-Methylxanthine and other xanthine derivatives have been shown various biomedical effects as adenosine antagonist and inhibitors of Primary Amine Oxidase [57,58]. Besides chemical synthesis, biotransformation and biosynthesis offered alternative way to produce 3-methylxanthine and other xanthine derivatives [22,48]. Due to theophylline degradation characteristic, A. ustus and A. tamarii would be applied in the production of 3-methylxanthine and xanthine with theophylline as feedstock through microbial conversion.…”
Section: Discussionmentioning
confidence: 99%
“…Several xanthine derivatives including 3-methylxanthine have been synthesized chemically for use in medical industry [47]. Except for engineering a microbial platform for de novo biosynthesis of diverse methylxanthins [48], bioconversion from cheaper feedstocks such as caffeine, theophylline and theobromine was an effective pathway to produce high value methylxanthines via metabolically engineered microorganisms [22]. In this study, 3-methylxanthine and xanthine were common and main products in theophylline degradation by A. ustus and A. tamarii.…”
Section: Production Of 3-methylxanthine or Xanthine Through Theophyllmentioning
confidence: 92%
“…129 In another study, focusing on the synthesis of methylxanthines in S. cerevisiae, higher methylxanthine production was observed when chromosomally introducing expression of biosynthetic enzymes compared with expression from a plasmid. 146 Recently, through testing truncated, weakened promoters to regulate the expression of antibiotic resistance markers, synthetic biologists were able to engineer high-copy plasmids into tunable-copy plasmids regulated by varying antibiotic concentration. 147 This strategy, named Pathway Optimization by Tuning Antibiotic Concentrations (POTAC), was utilized to enhance the titer of lycopene and n-butanol by 10-and 100-fold, respectively (to approximately 11 mg g À1 dry weight lycopene and approximately 110 mg L À1 n-butanol).…”
Section: Strategies For Gene Expression Tuning For Optimizing Phytochmentioning
confidence: 99%
“…Algharrawi et al (2015) reconstructed an engineering Escherichia coli with ndmA and ndmD gene from Pseudomonas putida, capable of producing 3-methylxanthine from exogenously fed theophylline[37] Mckeague et al (2016). engineered the eukaryotic microbial host Saccharomyces cerevisiae for the de novo biosynthesis of methylxanthines[38].…”
mentioning
confidence: 99%
“…Algharrawi et al (2015) reconstructed an engineering Escherichia coli with ndmA and ndmD gene from Pseudomonas putida, capable of producing 3-methylxanthine from exogenously fed theophylline[37] Mckeague et al (2016). engineered the eukaryotic microbial host Saccharomyces cerevisiae for the de novo biosynthesis of methylxanthines[38]. Additionally, 3-methylxanthine was main intermediate metabolite of theobromine through the initial demethylation at position N-7 by theobromine-degrading fungi[32].Because of dominant microbe in the solid-state fermentation causing the significant reduction of caffeine content, Pu-erh tea could be used to select effective stains converting theobromine to 3methylxanthine.…”
mentioning
confidence: 99%