From: ian@inf.ethz.ch (Ian)
Newsgroups: sci.nanotech
Subject: Re: Organic Machines?
Date: 25 Jan 93 22:25:48 GMT
Organization: Dept Biochemistry, University of Bristol, UK

In article <Jan.21.23.07.19.1993.5333@planchet.rutgers.edu> szabo@techbook.com (Nick Szabo) writes:
>
>The second is biotechnology, 
>with liposomes (drug-carrying artificial membranes), monoclonal 
>antibodies (cells programmed to be triggered by specific molecules), 
>polymerase chain reaction (self-replication of DNA outside the cell, 
>greatly accelerated over what nature can do), and gene-splicing
>as the basis for two new fields, protein engineering and metabolic
>engineering.

What do you refer to as 'metabolic engineering' ?  It's a new phrase to me.

>We can already see these two fields starting to merge.  Lithography
>is being used to program arrays of chemical reactions, for use
>in DNA sequencing, designer polymers, etc.  Enzymes (protein
>catalysts) have been built into clay structures; these molecular
>cyborgs now help make such ubiquitious products as the corn syrup in 
>your Pepsi.  Soon we will see enzymes designed on a computer,

I don't think that protein-design will become that advanced so soon.
The problem is terribly difficult, involving:

1) Analysis of biological catalysis (there are still only a few rigorously
   studied enzymes) and its extension to the design of general new catalysts.

2) Solving the problem of protein folding/protein local-conformation to the 
   point of being able to insert the desired arrangement of catalytic groups
   into a protein framework.

>programmed into DNA by wet-array-lithography,

Why not just use a gene-synthesizer, like we usually do ?

>mass produced by 
>gene-spliced bacteria, and then hooked onto lithographed structures
>to form catalysts orders of magnitude more proficient than today's.

It depends what you mean by 'proficient' ?  Existing enzymes are very
good catalysts but constrained by the fact that they were produced to meet
several other requirements besides their basic catalytic role.  For example,
they must be soluble, stable and must'nt bind irrevocably to other cell
components.  Also they must be specific to the desired reaction and must
ignore other, very similar compounds.  Some of they also incorporate
control mechanisms.

If we were to arrange things so that many of these additional requirements
were no longer necessary, then we probably could produce superior (=faster)
catalysts.  The question is:  would we want to ?

For example, specificity might be a very useful characteristic in an
industrial situation, why purify the output from one process when the next
could be made to ignore the impurities ?

I suspect that evolved enzymes (whilst not definitively 'best', that would be
an unreasonable expectation) are extremely good examples of the art of
catalysis and that we would be extremely hard-pushed to make more than
rudimentary improvements.




I guess my real reason for replying to this article was to say that the Nick
gave an impression of Biotechnology that was very close to being a general
technique for the design and construction of catalysts.  In fact, we are
still fumbling around at the edges.

I don't want to belittle biotech, however, the compounds that can be
specifically synthesized by biological methods are two orders of magnitude
more complex than those that can be made by chemical approaches (ie proteins
of mol.wt. 30,000 with every atom in the right place).  I just didn't want
anybody to expect too much too soon.