From: Aubrey de Grey (ag24@gen.cam.ac.uk)
Date: Sun Aug 31 2003 - 12:42:00 MDT
Robert Bradbury wrote:
> I don't think that is going to work Aubrey. Is it know for example
> that existing stomach enzymes don't break down the materials that you
> mention? The problem might end up being a lack of specificity or an
> inability to work at "normal" PH. In which case I don't think having
> more enzymes is going to do the trick -- it seems unlikely that nature
> would have evolved enzymes to deal with the specific materials but
> rather enzymes that are capable of breaking specific types of bonds.
> In which case their use might produce rather nasty side effects.
The ability of such things to be broken down in the stomach has not
been explored, no, but the place where their breakdown is attempted
and fails is the lysosome, which is a lot more acidic than the rest
of the cell (albeit not as acidic as the stomach). The specificity
problem sounds ominous, but in fact not: the reason bioremediation
is so successful is that wherever there is a high abundance in the
soil of something that's organic and energy-rich, micro-organisms
find a way to live off it -- the evolutionary pressure to do so is
strong, because if you're a slow-growing species you need something
that the faster ones lack. That's why you can find bacteria at the
roadside that can eat tyre rubber, for instance. So, graveyards are
quite likely to have microbes that can break down recalcitrant human
remains (except bone, of course, because bone isn't energy-rich.)
And then, of course, the specificity problem applies to the microbe
too -- it has to be impervious to its own enzymes. Of course there
will be times when something that's non-toxic to its host is still
toxic to us, but then we just keep looking for other enzymes. There
is also unlikely to be a pH problem with fungi, because they have an
equivalent of the lysosome.
> One might have to resort instead to "directed evolution" of the type
> that Maxygen does to get enzymes with the desired specificity. Or
> finally one might just have to do the enzyme tweeking "by hand" as
> was done to several of the DNA polymerases to get them to function
> more effectively in sequencing applications.
Both agreed, especially for baterial enzymes where the pH optimum is
likely to need changing. But one still needs to find the promising
enzyme to begin with -- and that's where the genomes can speed things
up.
> I think one may need to devote more attention to what lipofuscin
> really is (perhaps to the extent that they have studied what amyloid
> is) before one can effectively begin to take it apart.
Maybe, but maybe we'll find that evolution has given us the solution
without our needing to know how it did it. Same as for Chlamydomonas
nuclear-coded mitochondrial proteins that are mt-coded in animals.
Aubrey de Grey
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