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GM Organism Produces New Amino Acid
blamanj writes "Scientists led by Scripps Research Institute chemistry professor Dr. Peter Schultz have engineered a version of the E. coli bacteria that can produce an amino acid not found in nature. Story at the Environment News Service and Science Daily."
The majority of the nonstandard amino acids present in protein come about by post-translational modification; they start off as a standard amino acid and either are modified by another protein or are simply unstable in their environment as a standard amino acid. Oxidation of cysteines to cysteine sulfenic (-inic, or -onic) acids is one example, phosphorylation of tyrosines is another. Selenomethionine and selenocysteine are sometimes examples of this as well (enzymatic replacement of the sulfur with selenium), although in some special cases are coded in the DNA as specifically being selenomethionine and selenocysteine as opposed to methionine and cysteine. What the group at Scripps did was engineer E. coli to change how it recognizes a codon or a set of codons, presumably ones that E. coli rarely uses (can't find the original article, damnit!) and incorporate a new amino acid, p-aminophenylalanine in place of whatever normal E. coli put in a polypeptide before when it hit that codon. This is cool because previous efforts used modified growth media to "trick" the bugs into putting something similar in a protein in place of a standard amino acid whereas here the bugs are using 21 (23 if you're being tight with your definitions and including selenocysteine and selenomethionine) amino acids. The goal of the study is to try and look at why we've ~all got 20 (22) amino acids and not some other number. I wish them luck on that one, but at least they've got a start on the tools necessary to figure that out.
We could potentially develop proteins and enzymes not found in nature. That's a bit of a complex task right now, but it might be of use in 20-50 years once we have a better understanding of proteonics.
Even so, what ever happened to appreciation of scientific experimentation for its own sake? Why is the first post in almost any Slashdot article about pure science a question like, "Just what good is it anyway?" It's not like every scientific endeavor must produce marketable results immediately to be worth trying.
If it's for-profit but free, you're not the customer -- you're the product (e.g., the Slashdot Beta's "audience").
yeah, could build new or expensive-to-synthesize proteins with them, or even maybe even useful polymers.
By the way, there are different species of e. coli - there's a good one that actually is *supposed* to be in everyone's intestines....and yes, some bad ones that cause problems: read about that here
There's two more surprises in this pipeline that will be coming out of shultz group. this is the tip of the ice berg.
...) and thus can be given in lower doses and less frequently. Currently Most plausible protein therapeautics are not effective for exactly these reasons: they get digested two quickly or would have to be delivered in toxic doses. With the extremley large amino acid substitution set available, it would be theoretically possible to redesign drugs in a computer much faster than pathogenic organisms could evolve machinery to destroy each new variation.
First lets explain what shultz achieved that was new. with 4 bases there are 4^3 = 64 possible 3 base-codons. Think of these as the word (or byte) size used in computer that uses base-4 rather than base 2 logic. (so this is equivalent to a 6 bit byte). continuing this analogy, like the ascii character set, these bytes code for the 'amino acid' cheracter set.
However, these are non-uniquely mapped to 20 amino acids (plus an end-of-line character) by the ribosome. In keeping with the ascii analogy, more than one bit pattern is interpreted as the same letter. In principle one could have as many as 63 different amino acids represented in this coding scheme but in practice there are only 20.
Because nature designed ribosomes and tRNAs so long ago you just cant fiddle with this machinery very easily and expect any orgnaism to be viable. (sort of like messing with the lowest level of the bios). To fiddle with it successfully you would have to fiddle with many poorly understood parts simultaneously.
The above statement is almost true. There are a few organims that happen not to use one or two of the 64 codons. these codons are called amber and ochre in the literature. In such an organism these codons are "undefined" and not used anywhere in the DNA of the organism. (oversimplification warning).
If one edits the organism's DNA to add these codons into a gene, and also simultenouesly supplies the organism with the ability to translate these codons to a new amino acid, then you can get the organism to build proteins using 21 amino acids one of which is defined by you. By "simultenouesly supplies the organism with the ability to translate these codons" I mean specifically supplying the organism with the specially modified tRNA which has on one end the signal to recognize the new codon, and on the other end is a gripper that holds the synthetic amino acid.
This has been done many times previously. However in all these cases the magic tRNA is chemically synthesized and then 'fed' to the organism. Shultz's work here is to get the organism to do the synthesis of this amber recognizing tRNA and the new amino.
Shultz's group has something even more revolutionary in the pipeline. They are working on adding two more bases to the 4 base set of DNA.
this gives 6^3 = 216 codons. of which only 64 are currently spoken for with natural tRNAs. For practical purposes this is an unlimited number of novel amino acids that could be incorporated into a protein.
Actually If I remeber correctly they have already created a working 6 base DNA, as well as created tRNAs that a ribosome can use to generate proteins. So now 'all' they have to do (I guess) is incorporate the tRNA and non-natural amino acids synthesis into the bug itself. in the mean time they can of course do this synthetically and 'feed' the tRNAs to the bugs.
This is pretty damn exciting stuff. there are an amazing number of possible uses. I'll name two
first, protein's built from unusual amino acids will escape many cellular mechanisms for degrading or cutting up proteins. Medicines built out of these proteins will thus be able to last longer in the host (human or bacteria or
A second application is there is no limit to the chemical functionality that could be placed on the bussiness ends of these amino acids. This would probably be a bad idea for use as therapeuatics, but would be a great way to make chemically active self-assembling nano materials. We let e coli built rigid protein scaffolds in any shape we want and then use this tehcnology to put reactive chemicals at precise locations on the scaffold. You can think of this like designer molecular sized cresent wrenches that can be shaped and chemically coded to grip only certain other shapes. the old lock and key analogy.
It is a modest exaggeration to imagine not just molecular sized transistors, but entire self-assembling mulit-molecular sized circuits and logic gates. That's a ways off. Before we get there there will be other sorts of molecular sized self-assembled doodads from molecular machines to chemical processing systems to optical coatings to information storage.
Some drink at the fountain of knowledge. Others just gargle.