Complete biosynthesis of cannabinoids and their unnatural analogues in yeast

@article{Luo2019CompleteBO,
  title={Complete biosynthesis of cannabinoids and their unnatural analogues in yeast},
  author={Xiaozhou Luo and Michael A. Reiter and Leo d’Espaux and Jeff Y F Wong and Charles M. Denby and Anna Lechner and Yunfeng Zhang and Adrian T. Grzybowski and Simon Harth and Weiyin Lin and Hyunsu Lee and Changhua Yu and John Shin and Kai Deng and Veronica Teixeira Benites and George Wang and Edward E K Baidoo and Yan Chen and Ishaan Dev and Christopher J. Petzold and Jay D. Keasling},
  journal={Nature},
  year={2019},
  volume={567},
  pages={123-126}
}
Cannabis sativa L. has been cultivated and used around the globe for its medicinal properties for millennia1. Some cannabinoids, the hallmark constituents of Cannabis, and their analogues have been investigated extensively for their potential medical applications2. Certain cannabinoid formulations have been approved as prescription drugs in several countries for the treatment of a range of human ailments3. However, the study and medicinal use of cannabinoids has been hampered by the legal… 
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References

SHOWING 1-10 OF 42 REFERENCES
Identification of olivetolic acid cyclase from Cannabis sativa reveals a unique catalytic route to plant polyketides
TLDR
This work shows that a type III PKS (tetraketide synthase) from cannabis trichomes requires the presence of a polyketide cyclase enzyme, olivetolic acid cyclase (OAC), which catalyzes a C2–C7 intramolecular aldol condensation with carboxylate retention to form OA.
The draft genome and transcriptome of Cannabis sativa
TLDR
The availability of the Cannabis sativa genome enables the study of a multifunctional plant that occupies a unique role in human culture and will aid the development of therapeutic marijuana strains with tailored cannabinoid profiles and provide a basis for the breeding of hemp with improved agronomic characteristics.
Purification and Characterization of Cannabidiolic-acid Synthase from Cannabis sativa L.
TLDR
It is concluded that CBDA is predominantly biosynthesized from cannabigerolic acid rather than cannabinerolic acid, although the kcat for the former is lower than that for the latter, and that the enzymatic cyclization does not proceed via oxygenated intermediates.
The hexanoyl-CoA precursor for cannabinoid biosynthesis is formed by an acyl-activating enzyme in Cannabis sativa trichomes.
TLDR
It is suggested that CsAAE1 may have been recruited to the cannabinoid pathway through the loss of its PTS1, thereby redirecting it to the cytoplasm and suggesting that hexanoate may be formed through a pathway that involves the oxygenation and breakdown of unsaturated fatty acids.
The Medicinal Use of Cannabis and Cannabinoids—An International Cross-Sectional Survey on Administration Forms
TLDR
The survey was completed by 953 participants from 31 countries, making this the largest international survey on a wide variety of users of cannabinoid-based medicine performed so far, and in general, herbal non-pharmaceutical CBMs received higher appreciation scores by participants than pharmaceutical products containing cannabinoids.
Production of Δ9-tetrahydrocannabinolic acid from cannabigerolic acid by whole cells of Pichia (Komagataella) pastoris expressing Δ9-tetrahydrocannabinolic acid synthase from Cannabis satival.
TLDR
Whole cells of P. pastoris offer the capability of synthesizing pharmaceutical THCA production using whole cells, which prevents the THCAS application in aqueous cell-free systems.
The inheritance of chemical phenotype in Cannabis sativa L. (V): regulation of the propyl-/pentyl cannabinoid ratio, completion of a genetic model
TLDR
Inbred lines derived from multi-cross hybrid combinations reached unprecedented PC3 levels of up to 96 % which supports the hypothesis of the regulation of C3/C5 ratios, and a model of a multiple locus A1–A2–…An is proposed, with the pentyl- and propyl cannabinoid pathway being enhanced by alleles Ape1−n and Apr1–n, respectively.
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
TLDR
A comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy is provided.
...
...