Molecular Engineering of Yeast

Wait, this is your thread. Did you read the article? They are building the yeast genome from scratch. The first time it has been done on a eukaryotic organism. Read the 3rd and 5th paragraph.

Definitely synthetic. And with far greater implications than simply beer price and strength.

 

Bigger yeast infections.

 

As a former grad student, believe me when I say that beer drives the science of the future.

 

GAHHH BEAT ME TO IT. Thought I was so clever.......

Have you ever seen I Am Legend? I picture them being somewhat like that....

 

Shhh. Theyre on to us.

 

I agree with the waste of a food resource to make ethanol. Where I think GMO microbes have potential is in cellulosic ethanol. Generally, cellulose ("dietary fiber") can't be broken down except for a few very select microbes (bacteria in a termite's gut, for example). There are lots of interesting pilot projects to engineer microbes or enzymes to accomplish this. Use the corn kernel for food/feed; use the corn stalk for ethanol. I'd love to see this succeed.

 

I have little idea about the particulars of what you're talking about, but 100% applaud you for applying science here. people fear change which is where resistance to your ideas have come from.

keep on keeping on

 

UHG!!! It's beer!!! Water hops yeast malt. Scientist should study liver failure and beer gut reductions...that's what beer drinkers need from them! We already know how to make awesome beer! ;-) and no I did not do very well in science class.

 

I guess I should have specified the "this" that I was referring to. I was simply stating that it is unnecessary to engineer a yeast that survives higher alcohol percentages and makes beer cost less (see the point(s) that I originally gave). As I also stated in my original post, I have no problem with them trying to modify yeast in order to do other things such as those that the OP suggested or those that you have stated. I believe that those could be huge. I just don't think that was the main point of the article (and if it isn't the main point, then the title and most of the content is highly misleading).

 

My background is in organic chemistry, but I worked in a genetics lab as an undergraduate and I have a tremendous amount of interest and excitement regarding the work that is going on right now in this field. I would echo the sentiment that people that are scared of GMO are woefully ignorant - I don't think it's hyperbole to say that GMO could herald the second green revolution.

I'm not sure how much you've read on the subject, but I know researchers in China have been making GMO S. cerevisiae strains for about 6 years now. Their initial goal was to introduce genes from other fungi and bacterial species to make cerevisiae more adept at making fuel ethanol. Specifically, they introduced genes for a variety of beta-glycosidase enzymes so that the yeast could more efficiently utilize all the glucose present (from cellulose, cellobiose, and other normally unusable sugars). An unexpected side effect of this was that the yeast could now hydrolyze glycosides which were glycone/aglycone (i.e. a glucose beta-linked to a hop aroma terpenoid like linalool). Hops naturally produce a lot of glycosides, and in the past 4 years or so there has been a lot of research interest in figuring out whether they a "hidden" source of aroma in beer. Some work indicates that glycosides may be the source of "kettle hop flavor", where the normal aroma compounds are otherwise steam-distilled away up the kettle chimney.

None of these Chinese S. cerevisiae strains are in the US. No brewery I am aware of uses a GMO yeast. I think they'd get crucified if they even tried. There is a lot of resistance towards GMO in the US, and I think the vast majority of that resistance is completely unwarranted. Even though I like the "romantic" aspect of having a 300 year-old house yeast, there are a lot of very good things that good be done to produce a better fermenting engine. Pick a flaw - we could fix it. Some very simple things I would initially want out of a GMO yeast:

• Fix the downregulation of maltose/maltotriose transporters in the presence of glucose (fix glucose repression)
• Add a good beta-glycosidase enzyme to ensure glycoside hydrolysis
• Increase ethanol tolerance to ~20%. Not because we need to be making 20% beers, but because we would then have better cell viability for re-pitching.
• Fine tune/customize ester production.
• Lower higher-alcohol production (not much can be done about propanol, but I think we can lower butanol and up) .
• Fine tune/customize flocculation. Want a yeast that never settles so you can have a continuous fermentation like they're attempting at Weihenstephan? Fixed. Want a yeast that reliably flocculates and settles after X days? Fixed.
• Increase SO2 production. This molecule is one of the best endogenous antioxidants in beer and really stretches out the shelf life. Right now you have to stress your yeast out to coax increased production; it would be nice if the yeast just obliged without that requirement.

Just a few thoughts from a pro-GMO scientist. It's the future, and it's a good future, as long as we don't let fear, litigation, and antiquated copyright law screw everything up.

 

Yeast doesn't cost me a cent. I have various cultures which I re use when home brewing.

I'm sure BMC will be all over this. I doubt home brewers and craft breweries will use artificial yeast on a large scale.

Brewing is both art and science. To make a great beer, you need both.

 

oh no, this is going to sound terribly vague, but it was a long time ago, so here goes: I was a grad student in the early/mid 80s. Upstairs from me was a lab that did some work on yeast (but mainly E.coli and B subtilis); the PI was very well known as the R in pBR322. He had a visiting scientist from a brewery (can't remember which one, Carlsberg springs to mind) who was on a quest to isolate the gene for an enzyme that was responsible for making a chemical that was in their opinion, an off flavor. I don't know the flavor or the chemical or if they succeeded. So, folks have been doing these sorts of things perhaps longer than realized? And of course without mol bio, folks have been cultivating particular strains as house strains for years, right?

 

While this is a fun idea, what really needs to be done first is genomic sequencing of all current brewery strains, organismal level quantitative analysis mRNA transcripts and quantitative proteomics studies, and computational mapping of of all metabolic pathway networks.

Having altered promoters turn on and off for brute force alcohol production really won't be of any use unless we know WTF we are doing to the organism, and additionally, just turning genes on without alteration of compensating pathways may not improve traits, as thinking is less and less of one gene one function and more of a network/systems approach. Making a strong beer full of fusel alcohols or unpleasant esters wouldn't be nearly as cool as being able to craft unique yeast strains to do what we want on a flavor/taste and aroma level.

As someone in the tail end of their Biochemistry and Molecular Biophysics Ph.D. (Caltech) with a previous work history as an analytical chemist, molecular engineer (Engineering bacteria and yeast metabolism to make anti-cancer drugs and antibiotics, specifically polyketides) and former hop chemist, I think engineering of yeast strains would be very cool, however there are pitfalls (see above).

An alternate technique instead of synthesizing genomes from scratch would be directed evolution. Directed evolution takes existing biological platforms (bacteria, proteins, etc.) and introduces mutations (Random PCR, Gene Shuffling, UV Mutation, etc.) and selects for new traits via specific biological assays (e.g. Phage Display, GC-MS, absorbance assays), and has a track record of producing some incredibly important pharmaceutical and industrial enzymes/proteins/bacteria/yeast. Directed evolution has the one big advantage that pre-existing biological entities (yeast/bugs, etc.) can be used for evolution, which in some ways is much easier than synthesizing a genome from scratch.

Whole point was not to be a downer, as I agree that biological engineering is the future of yeast generation, but to provide some intellectual jumping off points.

 

File thread under: "Postgraduate Molecular Biology circle jerk"

 

Not sure why the big fascination with ethanol content. Rather have a good tasting beer with slight variations in ethanol content than an unpleasant beer with an accurate and precise ethanol level.

 

Definitely synthetic. Their trying to remove the "genomic fat" from the yeast strain and make it more amenable to future genetic modifications. Just knocking out single genes is pointless without apriori knowledge of their functions and the effects on metabolism as a whole, plus there is already a complete single gene saccharomyces cerivisae knock out collection for studying the effects of single knockouts.

I don't fear GMO, but Monsanto's ignorance scares the shit out of me.

 

I agree with you on one thing. GMO is very similar to "regular" breeding programs. Folks would be wise to lump them together, as they are basically the same.

I think the jury is still out on whether they should be feared, and in fact it is my belief that the breeding we embark on with little practical knowledge of consequences needs very much to be feared. Were we to argue this point I would merely point to how the consequences to nature of our technology, in general, have panned out so far as my side of the argument.