[DIYbio] Re: Some ideas for entrepreneurs

Hi Simon,

I think it's a great idea, and definitely it would be something you could do. In this case you could think of engineering these bugs to overexpress few of the essential genes involved in the metabolic pathway to DHA for example. Or introducig some heterologous genes to boost the yield.

There are two major constraints, they i like to define as "design constraints" in such system:

a) the organisms you'll probably work with will be coming from lab collections, otherwise you'll most likely have to go for an isolation study and to optimize a transformation system to introduce and keep stable the integrated DNA into one of the bugs in there. I talk about integrated DNA as plasmids would probably be lost soon. Integrative approaches are not always straightforward, yes now we have crispr, yet you'll need to find a working promoter and work on expression levels in that case.

b) evolutionary stability aka "why should i produce this?"
Algae have been shaped by the forces of evolution to store lipids in periods of low nitrogen/phosphate and high carbon abundance. After such stressful period they can digest them back and live off their stored energy. If you would express "n" gens in a different host this should match it's metabolism and confer a competitive advantage. This will probably reduce growth speed or resilience of the strain. The risk is tohaving it "washed out" of the gut system, unless it forces to stay through biofilm i guess. Anyway doubling by doubling the chance of mutation rate will accumulate leading one day to a loss-of-phenotype mutant.

So nature is pretty awesome and usually things that we think we could engineer in microbes are already happening somewhere else. Now im thinking: is there a similar bacteria already existing in nature? And can we find a way to introduce it in chickens?

Good idea btw, it's definitely an interesting approach.
Looking forward to see how this evolves.

Best,
Fede

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Re: [DIYbio] Some ideas for entrepreneurs

It probably will be better to first measure the level of omega-3 in your chicken's eggs. Then feed them some omega-3 and measure the difference.  

There are multiple reasons for doing that before any other research.

I would not take the statement of the food industry for granted. They are probably not required to prove that the eggs which are labeled with having extra omega-3 contain more of omega-3 than average eggs. And even if they do have more omega-3 I bet they are not required to prove that the difference is significant for human consumption. So the whole thing can be an ordinary supermarket pseudoscience. 

Also, you will figure out how much fatty acid your bacteria or algae has to produce to make a difference. 

And you will develop an analytical technic that can be used to measure the progress while approaching any of the directions.

On Fri, Dec 9, 2016 at 7:45 PM Simon Quellen Field <sfield@scitoys.com> wrote:
Gut bacteria already produce short chain fatty acids (acetate, propionate, and butyrate), which feed the host animal, and other gut microbes. Bacteria-produced butyrate is, in fact, the major nutrient for the cells lining the large intestine. However, these short chain fatty acids are produced by anaerobes, not the lactobacilli I was thinking about. I only mention them as an existence proof that fat-producing bacteria already exist in the gut.

Producing algae as a feedstock for chickens is already done, and is one of the reasons omega-3 rich eggs are more expensive. Having the chickens produce it in their crops from ordinary cheap food eliminates this extra step, and all of the plant and equipment needed to grow the algae. And since the probiotic bacteria are also only used as a feedstock, there is no regulation. Anyone can sell probiotic capsules without U.S. government interference, as long as they make no medical claims. And feedstocks for chickens are even more loosely regulated than human supplements.

I am not saying it will be an easy thing to do, however. Moving an entire pathway from one critter to another is a lot different than just adding a gene to a plasmid. But getting this group thinking about applications like this can generate other ideas, even if no one here can do the job.

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On Fri, Dec 9, 2016 at 1:02 PM, Dennis Oleksyuk <dennis@oleksyuk.me> wrote:

It probably would be much easier to modify algae to overproduce omega 3. It is also easier to get government approval because it is only used as a feedstock.

Someone correct me if I'm wrong, but making bacteria to produce any type of fat will require a lot of extra energy. Therefore it will experience high evolutionary pressure to disable that gene. Plus it will become a food for other bacteria.


On Fri, Dec 9, 2016, 9:55 AM Simon Quellen Field <sfield@scitoys.com> wrote:
I raise chickens.
Some of them are Aracanas and Americanas, which lay eggs that are pale blue or green.
We joke about eating the green eggs with ham.

Chickens have a sac at the beginning of the digestive tract called a crop, where ruminant-like bacteria (lactobacilli, coliforms, and streptococci) help to digest food before it gets to the acidic stomach. At the other end of the digestive tract, they also have a caeca, where anaerobes live, just like in humans and cows.

Chickens only have one exit shared between the digestive system and the reproductive system. Thus the eggs pass through the same exit that the anaerobic microbes do.

Suppose someone were to feed the chicken some probiotic bacteria that expressed green or red fluorescent protein attached to a protein they excrete, so it attaches to the eggshell as it passes through. Now we get fluorescent green or red eggs.

The second idea is more practical, if less fun. Chickens are often fed foods high in omega-3 fatty acids, so that the eggs will also be rich in these beneficial fats. The sources of these fats are algae, which have the mechanisms for making them, which is why our main sources of DHA and EPA are fish oils, since the primary food source is algae.

Suppose someone engineered probiotic lactobacilli with a pathway for creating omega-3 fats stolen from marine algae, and we could feed this to chickens, so they produce their own omega-3 fats in their crop? This could dramatically lower the cost of omega-3 rich eggs, since the fats would not have to be added to the feed. It may also be possible to find a way to allow the original algae to grow in the crop, either by genetic modification or by changing the crop ecology so that other commensal organisms provide the nutrients the algae need to grow in the dark.

The nice thing about both of these modifications is that the chicken is not modified, and what we are feeding them has a friendly name -- "probiotics". These two things make it easier to market the resulting product.

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