Complete biosynthesis of cannabinoids and their unnatural analogues in yeast

Luo, Xiaozhou; Reiter, Michael; d’Espaux, Leo; Wong, J.Y.C.; Denby, Charles M.; Lechner, Anna; Zhang, Yunfeng; Grzybowski, Adrian T.; Harth, Simon; Lin, Wan-Ying; Lee, Hyunsu; Yu, Changhua; Shin, John H; Deng, Kai; Benites, Veronica T.; Wang, George; Baidoo, Edward E. K.; Chen, Yan; Dev, Ishaan; Kim, Young-Mo; Keasling, Jay D.

doi:10.1038/s41586-019-0978-9

Cited by 532 publications

(526 citation statements)

References 33 publications

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“…The race to develop high‐yield, ethanol‐producing yeast strains for the biofuel industry is led by large companies such as Lallemand, DuPont, and Novozymes. Pioneering work has successfully engineered S. cerevisiae to produce plant‐derived therapeutics including the antimalarial drug artemisinin (Paddon et al, ); the cancer therapeutics taxol, noscapine, and taxediene (Ding et al, ; Li et al, ); and endocannabanoid and opioid analgesics (Galanie et al, ; Luo et al, ; Zirpel, Degenhardt, Martin, Kayser, & Stehle, ). Cao et al () designed a P. pastoris platform to produce multiple biologics in a single strain or in co‐cultures of two strains, and as a proof of principle, they produced and isolated three protein biologics.…”

Section: Yeasts Have a Large And Growing Role In The Emerging Bioeconomymentioning

confidence: 99%

“…Synthetic biology is a discipline that combines biology, nanotechnology, and engineering to design and build novel organisms and systems. The ability to integrate heterologous genes and to delete, upregulate, or downregulate native genes made it possible to engineer pathways that reshape the metabolism and extend the substrate (e.g., D-xylose; Wasserstrom et al, 2018) and product ranges of yeast strains, (cannabinoids and opioids; Galanie, Thodey, Trenchard, Filsinger Interrante, & Smolke, 2015, Luo et al, 2019.…”

Section: Synthetic Biology Approaches To Create Whole Pathway and Rmentioning

confidence: 99%

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The renaissance of yeasts as microbial factories in the modern age of biomanufacturing

Payen

Thompson

2019

Yeast

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Yeasts are essential for many processes, including the production of some of our most beloved foods and beverages. Less is known to the public about the far‐reaching impacts of yeasts on other products such as biofuels, pharmaceuticals, and industrial products. By leveraging and combining newly discovered yeast genetic diversity with now affordable and efficient genetic engineering and synthetic biology tools, academic and industrial yeast labs have designed yeast cell factories for a wide range of novel applications such as the production of medicines, components of human breast milk, heme for meat substitutes, bioplastics, and other biomaterials. This review covers the newest technologies developed for yeast research including synthetic biology and their use in the engineering of yeast cell factories for emerging applications.

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Section: Yeasts Have a Large And Growing Role In The Emerging Bioeconomymentioning

confidence: 99%

Section: Synthetic Biology Approaches To Create Whole Pathway and Rmentioning

confidence: 99%

The renaissance of yeasts as microbial factories in the modern age of biomanufacturing

Payen

Thompson

2019

Yeast

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“…Saccharomyces cerevisiae is one of the most widely used microbial hosts in biotechnological 45 processes and has been engineered to produce a variety of industrially relevant compounds ranging from 46 pharmaceuticals to biofuels [1][2][3][4]. Production strains are typically engineered and optimized in small scale 47 cultivations, while the bioproduction processes take place in large scale bioreactors.…”

Section: Introduction 44mentioning

confidence: 99%

Population dynamics analysis ofSaccharomyces cerevisiaedeletion library during fed-batch cultivation using Bar-seq

Wehrs

Thompson

Banerjee³

et al. 2020

Preprint

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25To understand the genetic basis of changes in strain physiology during industrial fermentation, and the 26 corresponding roles these genes play in strain performance, we employed a barcoded yeast deletion 27 library to assess genome-wide strain fitness across a simulated industrial fermentation regime. Our results 28 demonstrate the utility of Bar-seq to assess fermentation associated stresses in yeast populations under 29 industrial conditions. We find that mutant population diversity is maintained through multiple seed trains, 30 enabling for large scale fermentation selective pressures to act upon the community. We identify specific 31 deletion mutants that were enriched in all processes, independent of the cultivation conditions, which 32 include MCK1, RIM11, MRK1, and YGK3 that encode homologues of mammalian glycogen synthase kinase 33 3 (GSK-3). Further, we show that significant changes in the population diversity during fed-batch 34 cultivations reflect the presence of significant external stresses, such as the accumulation of the 35 fermentative byproduct ethanol. The mutants that were lost during the time of most extreme population 36 selection suggest that specific biological processes may be required to cope with these specific stresses. 37Overall our work highlights a promising avenue to identify genetic loci and biological stress responses 38 required for fitness under industrial conditions. 39 40 41 42 43 124 125

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“…[29] (À)-CBD and its structural analogs, like other phytocannabinoids, have generally been obtained by the purificationa nd isolation from a Cannabis extract, yet challenging due to the structural, physical, and chemical similarities amongt he phytocannabinoids. [30] Therefore, chemical synthesis has its own advantages, considering practical difficulties in purificationa nd consistentq uality control (QC). For example, the absolutea nd relative chemical compositions in the Cannabis extracts are different from-strain-to-strain and from-harvest-to-harvest, making the QC for pharmaceutical grade practically difficult and costly marketwise.…”

Section: Introductionmentioning

confidence: 99%

Synthetic Strategies for (−)‐Cannabidiol and Its Structural Analogs

Jung

Lee

Jungnam

et al. 2019

Chemistry An Asian Journal

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À)-Cannabidiol ((À)-CBD), an on-psychoactive phytocannabinoid from Cannabis,a nd its structural analogs have received growinga ttention in recent years because of their potentialt herapeutic benefits, including neuroprotective, anti-epileptic,a nti-inflammatory,a nxiolytic, and anticancer properties. (À)-CBD and its analogs have been obtained mainly based on extraction from the natural source; however,t he conventional extraction-based methods have some drawbacks, such as poor quality controla long with purification difficulty.C hemical-synthetic strategies for (À)-CBD could tackle these issues, and, additionally,g enerate novel (À)-CBD analogs that exhibit advanced biological activities. This review concisely summarizes the historic and recent milestones in the synthetic strategies for (À)-CBD and its analogs.

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Complete biosynthesis of cannabinoids and their unnatural analogues in yeast

Cited by 532 publications

References 33 publications

The renaissance of yeasts as microbial factories in the modern age of biomanufacturing

The renaissance of yeasts as microbial factories in the modern age of biomanufacturing

Population dynamics analysis ofSaccharomyces cerevisiaedeletion library during fed-batch cultivation using Bar-seq

Synthetic Strategies for (−)‐Cannabidiol and Its Structural Analogs

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