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"the feasibility of engineering heterologous production of kavalactones in yeasts and bacteria"

TheKavaSociety

New Zealand
Kava Vendor
Might be of interest to those who actually understand this stuff:

https://www.biorxiv.org/content/early/2018/04/04/294439

Abstract:
For millennia, humans have used plants for medicinal purposes. However, our limited understanding of plant biochemistry hinders the translation of such ancient wisdom into modern pharmaceuticals. Kava (Piper methysticum) is a medicinal plant native to the Polynesian islands with anxiolytic and analgesic properties supported by over 3,000 years of traditional use as well as numerous recent clinical trials. The main psychoactive principles of kava, kavalactones, are a unique class of polyketide natural products known to interact with central nervous system through mechanisms distinct from those of the prescription psychiatric drugs benzodiazepines and opioids. Here we report de novo elucidation of the biosynthetic pathway of kavalactones, consisting of seven specialized metabolic enzymes. Based on phylogenetic and crystallographic analyses, we highlight the emergence of two paralogous styrylpyrone synthases, both of which have neofunctionalized from an ancestral chalcone synthase to catalyze the formation of the kavalactone scaffold. Structurally diverse kavalactones are then biosynthesized by subsequent regio- and stereo-specific tailoring enzymes. We demonstrate the feasibility of engineering heterologous production of kavalactones and their derivatives in bacterial, yeast, and plant hosts, thus opening an avenue towards the development of new psychiatric therapeutics for anxiety disorders, which affect over 260 million people globally.
 

verticity

I'm interested in things
This is pretty amazing stuff. I don't understand it completely, but I'll attempt a brief English language explanation of the parts I do understand.

First a little background. The chemicals produced within living things are naturally made in roughly the following way:

- Information from the DNA in the nucleus is copied to RNA which carries the information out of the nucleus.
- The information in the strands of RNA is then translated into sequences of amino acids, which are strung together to make proteins.
- Proteins have many functions. Some of the proteins are enzymes, which are basically little machines that are able to make all kinds of other chemicals, such as kavalactones.

So then what they did in this paper is identified some of the specific sequences in the DNA of kava plants that are responsible for making the enzymes that in turn synthesize kavalactones. They inserted copies of these genetic sequences into other organisims, including other plants, bacteria and yeast, and were able to get those organisms to produce kavalactones and related chemicals. (In particular, they got E. coli and yeast to make bisnoryangonin, which is a KL similar to yangonin...is has -OH groups where yangonin has methoxys)
 
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The Kap'n

The Groggy Kaptain (40g)
KavaForums Founder
This is pretty amazing stuff. I don't understand it completely, but I'll attempt a brief English language explanation of the parts I do understand.

First a little background. The chemicals produced within living things are naturally made in roughly the following way:

- Information from the DNA in the nucleus is copied to RNA which carries the information out of the nucleus.
- The information in the strands of RNA is then translated into sequences of amino acids, which are strung together to make proteins.
- Proteins have many functions. Some of the proteins are enzymes, which are basically little machines that are able to make all kinds of other chemicals, such as kavalactones.

So then what they did in this paper is identified some of the specific sequences in the DNA of kava plants that are responsible for making the enzymes that in turn synthesize kavalactones. They inserted copies of these genetic sequences into other organisims, including other plants, bacteria and yeast, and were able to get those organisms to produce kavalactones and related chemicals. (In particular, they got E. coli and yeast to make bisnoryangonin, which is a KL similar to yangonin...is has -OH groups where yangonin has methoxys)
Thank you verticity. I had trouble with this article. I understood a couple of words in there.
 
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