I would like to point member of this group to the following site where a
Larry Wackett discusses directed evolution for proteins. The site is
http://biosci.cbs.umn.edu/class/bioc/5309/1997/discussion/0040.html
Here is the text of his message:
Directed Evolution
Larry Wackett
Sat, 06 Sep 1997 01:02:00 -0500
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I had talked about a conference on Directed Evolution of Industrial
Enzymes just before leaving for it. It lived up to its billing I
thought. There was a good mix of theory and applications, between
academic and industry participants. It emerged that there is still much
to know about the course of protein evolution in nature. For example,
it is understood that the number of possible permutations of sequence
for even a small protein in enormous. So even mutating an existing
protein in the laboratory quickly becomes a very big task if one wants
to start changing 3,4, or 5 residues to all other possible amino acids.
So, that underlies the approach of using directed evelotion to cover a
lot of possibilities and screening or selection to identify some
desirable protein(s) that result. But how many mutant proteins have to
be screened to give you something you want?
The answer surprised me, in that the number was not that large. In a
number of examples given, screening 1000 or 10,000 mutants gave one or
multiple desirable new proteins. This seems like a pretty high success
rate and protends that these techniques will be used more commonly in
the future. The question also came up as to how many pathways through
sequence space would one take if the mutation and selection process were
done over and over. Interestingly, in one case where that was done,
many of the same mutations came up repeatedly. This suggests that there
are real hot spots for mutation, perhaps even that favorable ones are
selected for by some unknown mechanism. Overall, it was quite
entertaining and thought-provoking. It really showed that interst in
Microbial Biocatalysis is high in industry! That's certainly nice in
the context of this course.
Larry Wackett
glenn
see http://www.flash.net/~mortongr/dmd.htm
for lots of creation/evolution information
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