A Look at Chemical Biology
23/09/10 14:09 Filed in: GenomeWeb Daily Scan
Submitted by S. Pelech - Kinexus on Thu, 09/23/2010 - 14:09.
As enthusiasm for nanotechnology grows, it will become pretty apparent that the most facile strategy for adding functionality to microscopic structures is to reverse engineer from ourselves. As we learn more about our own molecular biology, as amazing as it is, it is clearly not that efficient.
For one example, we generate at least 30 times more DNA than what we need in our chromosomes. Easter lilies, butterflies and lungfish produce 31- to 48-times more DNA than we do in their chromosomes. In another example, we phosphorylate our proteins at as many as 700,000 phospho-sites, which is probably 100 times more than what is necessary for optimal cellular regulation. These processes have very high energy and material resources requirements, in particular with the consumption of adenosine-triphosphate. ATP is the main source of energy to drive all biological chemical reactions either directly or indirectly.
Nature has to start with what it has and then in a very haphazard way fumble into improved structures for proteins that have to serve structural and catalytic functions. Bacteria are more highly evolved from a molecular perspective than mammals, so their cellular processes are often more efficient. This is because the optimization that works with natural selection operates much faster in life forms that can reproduce in half an hour compared to those that may take decades.
Enzymes may be viewed as "molecular robots" that can be reprogrammed with slight mutations to adopt new functionalities or even tailored to work better. I believe that enzymes such as genetically engineered protein kinases will eventually become basic components in the design of nanoprocessors to drive computers in the not so far future. This might be partly achieved, for example, by creation of eukaryotic-like kinase signalling systems in prokaryotes that terminate in the regulation of chemoluminescent reporter genes.
While there has been some interest in using aptamers with oligonucleotides as biological catalysts, I suspect that this is unlikely to be a fruitful direction. It may have been at onetime that life was based in an RNA world. However, nature obviously found proteins to be much more efficient biological catalysts. With RNA (or DNA), four types of oligonucleotides serve as the building blocks for long polymers that twist and fold to adopt functional structures. With proteins, we have 20 types of common amino acids, which are slight smaller than the oligonucleotide bases, to use as building blocks for much greater versatility. It seems that oligonucleotides work best in an information storage capacity or as scaffolds for binding functional proteins.
The genetic code used by all known life on this planet uses 61 triplets of four base nucleotides to specify 20 common amino acids. However, there are hundreds of possible amino acid structures. Moreover, it is already feasible to re-engineer tRNA's so that 63 different tRNA's can specify 63 different amino acids, i.e. the 20 common amino acids plus 43 new amino acids and a still leave a stop codon. As we exploit this possibility, this will markedly expand the potential for bio-engineering and permit the synthesis of even more durable and robust proteins. Where this will go in terms of synthetic life enters into the realm of science fiction and human imagination.
Link to the original blog post.
As enthusiasm for nanotechnology grows, it will become pretty apparent that the most facile strategy for adding functionality to microscopic structures is to reverse engineer from ourselves. As we learn more about our own molecular biology, as amazing as it is, it is clearly not that efficient.
For one example, we generate at least 30 times more DNA than what we need in our chromosomes. Easter lilies, butterflies and lungfish produce 31- to 48-times more DNA than we do in their chromosomes. In another example, we phosphorylate our proteins at as many as 700,000 phospho-sites, which is probably 100 times more than what is necessary for optimal cellular regulation. These processes have very high energy and material resources requirements, in particular with the consumption of adenosine-triphosphate. ATP is the main source of energy to drive all biological chemical reactions either directly or indirectly.
Nature has to start with what it has and then in a very haphazard way fumble into improved structures for proteins that have to serve structural and catalytic functions. Bacteria are more highly evolved from a molecular perspective than mammals, so their cellular processes are often more efficient. This is because the optimization that works with natural selection operates much faster in life forms that can reproduce in half an hour compared to those that may take decades.
Enzymes may be viewed as "molecular robots" that can be reprogrammed with slight mutations to adopt new functionalities or even tailored to work better. I believe that enzymes such as genetically engineered protein kinases will eventually become basic components in the design of nanoprocessors to drive computers in the not so far future. This might be partly achieved, for example, by creation of eukaryotic-like kinase signalling systems in prokaryotes that terminate in the regulation of chemoluminescent reporter genes.
While there has been some interest in using aptamers with oligonucleotides as biological catalysts, I suspect that this is unlikely to be a fruitful direction. It may have been at onetime that life was based in an RNA world. However, nature obviously found proteins to be much more efficient biological catalysts. With RNA (or DNA), four types of oligonucleotides serve as the building blocks for long polymers that twist and fold to adopt functional structures. With proteins, we have 20 types of common amino acids, which are slight smaller than the oligonucleotide bases, to use as building blocks for much greater versatility. It seems that oligonucleotides work best in an information storage capacity or as scaffolds for binding functional proteins.
The genetic code used by all known life on this planet uses 61 triplets of four base nucleotides to specify 20 common amino acids. However, there are hundreds of possible amino acid structures. Moreover, it is already feasible to re-engineer tRNA's so that 63 different tRNA's can specify 63 different amino acids, i.e. the 20 common amino acids plus 43 new amino acids and a still leave a stop codon. As we exploit this possibility, this will markedly expand the potential for bio-engineering and permit the synthesis of even more durable and robust proteins. Where this will go in terms of synthetic life enters into the realm of science fiction and human imagination.
Link to the original blog post.