Re: [DIYbio] Increasing production of compounds already present in a plant?

8:21 PM |

Dakota has made a very nice summary of the main considerations. Admirably brief while being technically correct! Very nice job!
Andrew your original question is excellent and the field of metabolic engineering - whether improving endogenous production or transgenic production is very complex technically. But also a huge opportunity both scientifically and commercially.
>matt
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Dakota Hamill <dkotes@gmail.com> wrote:

There isn't an easy answer to your questions.  If you can figure out an easy answer, congratulations you have a billion dollar company.  Someone could spend an entire PhD thesis on figuring out how to optimize one single biosynthesis pathway for one end product, and people do.  There are companies that spring up with millions in funding that seek to make bio-synthetic pathways economically/commercially feasible for the production of certain small molecules.  It takes a lot of tweaking.  You have to consider many things.

1) the metabolic demand on the cell to produce your end product, as well as its toxicity (if any)
2)codon optimization for the enzymes necessary for each step of your reaction (rare codons can decrease how much of the necessary enzymes are made)
3) side-reactions which will "steal" your substrate or its intermediates along the way to the desired final product
4) expression of your desired enzymes in correct ratios (ie - you could put the different enzymes under the control of well characterized promoter and RBS with varying degrees of expression).  Some enzymatic reactions could be a bottleneck, so if you could pinpoint that, and increase the expression level selectively of that one enzyme, you could increase the efficiency of your pathway. 
5) Is all the work you put going to be worth it?

As an example, caffeine is probably a poor target molecule, but I understand you are probably asking to use it as an example.   So much of it is already harvested from coffee beans that it'd be a waste of resources to try to produce it in another organism.

A few companies try to do things like which you are speaking, I'm sure there are many more but these are just a few names I remember

http://www.bio-amber.com/products/en/products/succinic_acid   although I think they might just isolate it from agro waste products

I'm sure the caffeine biosynthesis pathway is well documented, so read journal articles about it to familiarize yourself with some of the genetic engineering tools they use, and then, apply it to a compound with a commercial value that is expensive to produce synthetically and could be an ideal target for production recombinantly.   1,000,000,000x easier said than done.

Also your idea of "feeding" an intermediate to an organism over-expressing a necessary enzyme to catalyze a final step to a finished product isn't lazy, it's a good idea.  People do it.  If there is a complex reaction that an enzyme can do well, which synthetic organic chemists can't match, sometimes its commercially viable to feed the organism an intermediate and let it spit out the finished product.

If you're dead-set on plants, metabolix is probably the closest thing you're looking for since they use plants.

There was another company that uses plant tissue culture to make Taxol intermediates but I forget the name of it. 




On Sat, Jun 21, 2014 at 4:47 PM, Andrew Willoughby <andrew.willoughby369@gmail.com> wrote:

How would you get a plant to produce more of a compound? Increasing the amount of caffeine in coffee, antioxidant anthocyanins in berries, or even that cyanide precursor in apple seeds?

I'm assuming that it depends on how the chemicals are produced in the plant of course. When I googled caffeine biosynthesis for instance, I saw that it involves several different steps. I'm guessing if you're using genetic engineering techniques it'll be hard to figure out exactly where your production is bottling up, but still the idea would be to increase the amounts of the enzymes needed in caffeine's sake at least to produce theobromine and turn it into caffeine. And I thought that you could increase the amounts of the enzymes (N-methyltranferases I think is what i read and add theobromine to the plant and let it turn that into theobromine into caffeine, but that's lazy! :D. How do you get an organism to produce more of an enzyme? Or I guess more completely, I don't want to know how to add a new biosynthetic pathway, but to increase the efficiency of one already present. I guess if it's too specific to the pathway in question, then stick with caffeine. Anthocyanins sound too tricky from Wikipedia (several enzymes at once) and I'm not interested in poisoning anyone so apples won't be much use.

Also slightly unrelated question but I don't really want to be making two posts and it's in the same vein, genetic engineering and compounds that plants produce, but if a plant produces a chemical in only its roots, or its leaves or its fruits, how would you get it to produce that compound in other parts of the plant? Is that a function of epigenetics? I'm thinking of things plants produce like insecticides and aromatic compounds.

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