Bioengineering studies and pathway modeling of the heterologous biosynthesis of tetrahydrocannabinolic acid in yeast

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dc.contributor.authorThomas, Fabian
dc.contributor.authorSchmidt, Christina
dc.contributor.authorKayser, Oliver
dc.date.accessioned2021-06-07T05:51:27Z
dc.date.available2021-06-07T05:51:27Z
dc.date.issued2020-10-12
dc.description.abstractHeterologous biosynthesis of tetrahydrocannabinolic acid (THCA) in yeast is a biotechnological process in Natural Product Biotechnology that was recently introduced. Based on heterologous genes from Cannabis sativa and Streptomyces spp. cloned into Saccharomyces cerevisiae, the heterologous biosynthesis was fully embedded as a proof of concept. Low titer and insufficient biocatalytic rate of most enzymes require systematic optimization of recombinant catalyst by protein engineering and consequent C-flux improvement of the yeast chassis for sufficient precursor (acetyl-CoA), energy (ATP), and NADH delivery. In this review basic principles of in silico analysis of anabolic pathways towards olivetolic acid (OA) and cannabigerolic acid (CBGA) are elucidated and discussed to identify metabolic bottlenecks. Based on own experimental results, yeasts are discussed as potential platform organisms to be introduced as potential cannabinoid biofactories. Especially feeding strategies and limitations in the committed mevalonate and olivetolic acid pathways are in focus of in silico and experimental studies to validate the scientific and commercial potential as a realistic alternative to the plant Cannabis sativa.en
dc.identifier.urihttp://hdl.handle.net/2003/40239
dc.identifier.urihttp://dx.doi.org/10.17877/DE290R-22112
dc.language.isoende
dc.relation.ispartofseriesApplied microbiology and biotechnology;104
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCannabis sativala
dc.subjectCannabinoidsen
dc.subjectTetrahydrocannabinolen
dc.subjectCannabidiolen
dc.subjectSynthetic biologyen
dc.subjectBioengineeringen
dc.subjectNatural Product Biotechnologyen
dc.subjectNphBen
dc.subjectCsPTen
dc.subject.ddc660
dc.titleBioengineering studies and pathway modeling of the heterologous biosynthesis of tetrahydrocannabinolic acid in yeasten
dc.typeTextde
dc.type.publicationtypearticlede
dcterms.accessRightsopen access
eldorado.secondarypublicationtruede
eldorado.secondarypublication.primarycitationThomas, F., Schmidt, C. & Kayser, O. Bioengineering studies and pathway modeling of the heterologous biosynthesis of tetrahydrocannabinolic acid in yeast. Appl Microbiol Biotechnol 104, 9551–9563 (2020)de
eldorado.secondarypublication.primaryidentifierhttps://doi.org/10.1007/s00253-020-10798-3de

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