
20n (YC W15) Uses Software To Engineer Microbes For Chemical-Making - saurabh20n
http://techcrunch.com/2015/02/26/20n/
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saurabh20n
Founder here; working on software that exploits the full potential of
engineered microbes; we're using them to make therapeutics, plastics,
materials, etc. happy to answer any questions.

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durkie
this sounds amazing! aside from the organics-only requirement (which makes
sense to me), what other limitations are there on what you can make? or is
everything basically open given a long enough search?

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saurabh20n
Many limitations! Constructing the designs (i.e., going from data->dna->cells)
takes time and is expensive: we pay vendors for the construction. So we have
to restrict our software to output designs that yield the most novel products,
with the least change to the biology of the microbe.

Most of the time changes do nothing! But if our models are accurate enough,
the engineering can be predictable. We are continuously improving our models
-- from more data mining, and from feedback from experiments.

That said, what our algorithm predicts right now is still a huge space
(5000-10000 products). That is the tree image in the article. For context, the
chemical industry centers around 70,000 products.

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levlandau
Really cool. Question: Assuming that your algorithms will become known or can
be replicated, how do you think about your defensibility? What is proprietary
here that improves via network effects? How does the licensing model work and
what are some comparable (old school/current) companies?

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saurabh20n
Defensibility for us: microbes we build, and the platform they form. Our
software-driven engineering is significantly faster than the state-of-the-art:
human's looking at metabolic maps. People will start building on top of our
initial microbes and improving them. These initial microbes form the
"platform" from which to enable more bioproduction apps.

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kanzure
> Defensibility: .... People will start building on top of our initial
> microbes and improving them. These initial microbes form the "platform" from
> which to enable more bioproduction apps.

That's not a very fair answer. I have often said pretty much that and was
laughed out of the room. Granted, maybe it's all in the delivery.

Microbes can be easy to culture and store, so that doesn't really count as
defensibility... and the software can't either, because nobody these days is
really struggling to run algorithms over regulatory networks or KEGG or
whatever...

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red_dazzler
There is already a lot of competition here (which is not necessarily a bad
thing)...will be interested to see how 20n can differentiate and or add value
upon what already exists.

[http://www.nature.com/nrmicro/journal/v10/n3/fig_tab/nrmicro...](http://www.nature.com/nrmicro/journal/v10/n3/fig_tab/nrmicro2717_T1.html)
[http://www.ncbi.nlm.nih.gov/pubmed/25080239](http://www.ncbi.nlm.nih.gov/pubmed/25080239)
[http://www.biomedcentral.com/1752-0509/5/122](http://www.biomedcentral.com/1752-0509/5/122)
[http://www.ncbi.nlm.nih.gov/pubmed/24642060](http://www.ncbi.nlm.nih.gov/pubmed/24642060)

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saurabh20n
Indeed! We love this community [1]. We started 20n with DARPA's help, in part
to gather more steam around the accuracy of software predictions tools within
synthetic biology. You seem to have worked on these tools, and so must know
the pain of convincing wet-lab scientists to follow up on the sw predictions.

Paracetamol, both for academics and to pharma, was a non-biosynthesizable
molecule. But once we had the prediction, we were able to go to the lab to
construct the microbe pretty easily.

In the end, the tool is the start of the process. We are investing significant
resources in constructing the microbes. Over the coarse of the next two year,
hopefully you will find some novel molecules in the ones we move to
bioproduction.

[1] Have to! We are part of it. :) We know most of them, and they probably
know us.

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jjoonathan
Cool! I almost went into a lab studying polyketide synthase enzymes. How
heavily do they feature in your pathways? Is their modularity
overstated/understated?

(I fully intend to stalk you on google scholar after I get back to the things
I really ought to be working on right now...)

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saurabh20n
Hah! Oh PKS-es! Megasynthases (PKS, NRPS, FAS) do not currently feature very
heavily in our algorithms, but their modeling is certainly within our intended
algorithmic expansion plans. As for whether they are understated/overstated,
my cofounder can sit you down for hours and speak about them, but you have
probably moved on!

ps: Googling me will lead you to program synthesis: programs that program
programs :) which is another curiosity that you may or may not want to dive
into. You will find a lot more biology from my cofounder. google scholar:
chris anderson synthetic biology.

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blacksmith_tb
Question: could these be tailored for end-users? So instead a prescription a
patient could be sent home with a jar of pickles that synthesized their
medication as they fermented? I could see that disrupting the pharmaceutical
industry (if dosage could be controlled).

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aareet
This is really interesting - this field is new to me, but is there existing
research available that shows that this works for large scale chemical
production or will this be something that you'll be working on inventing?

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saurabh20n
Optimizing for large scale production is indeed what most of the field works
on. There have been many success stories: an anti-malarial drug through yeast
(Artemisinin by Amyris+Sanofi), a plastic precursor through bacteria (1,4-BDO
by Genomatica+DuPont), and more.

What they are missing is the whole spectrum of what could be made
biologically. We will create microbes for the most valuable chemicals and then
partner with existing optimization companies that have industrial fermenters
running. Think beer fermentation, just instead of the alcohol yeast, you use
our yeast.

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foobarqux
Really interesting, but the article doesn't explain why someone would want to
grow chemicals using microbes instead of synthesizing them through chemistry.
Is it cheaper?

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saurabh20n
Yes. When going after non-trivial chemicals the economics work out, and is
cheaper when scaled up. The process essentially repurposes beer fermentation.
The usual benefits of biological production: carbon-negative, and not using
any toxic catalysts or producing waste products hold as well. Consider the
molecule, paracetamol/acetaminophen/Tylenol [1], that we created a microbe
for: The US alone produces 35000+ tonnes of it, all currently coming from
petro-routes. It would be nicer to get it the same way we get beer, if we
could.

There might be additional market forces that make a microbial fermentation
attractive: e.g., in the case of the anti-malarial drug artemisinin,
fluctuation in supply of the plant Artemisia annua, the price of the drug
varied between $120-$1200/kg, and Amyris and Sanofi moved it to yeast based
production for creating a steady supply [2]. That route was critical for the
supply of the drug to African countries.

For many of the requests we get, chemical synthesis is not economically
feasible to take the chemical to market, and bioproduction might be the only
route. The fact that we suggest routes that work well for the planet is a good
side-effect. :)

[1]
[http://en.wikipedia.org/wiki/Paracetamol#Synthesis](http://en.wikipedia.org/wiki/Paracetamol#Synthesis)

[2]
[http://en.wikipedia.org/wiki/Artemisinin#Synthesis_in_engine...](http://en.wikipedia.org/wiki/Artemisinin#Synthesis_in_engineered_organisms)

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prenschler
are you hiring? and what for?

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saurabh20n
Tech people. Ideally, somebody with algorithms chops, but one who doesn't get
scared by biology or chemistry.

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prenschler
How do we apply?

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saurabh20n
email me: info@20n.com

