4th EucheMs chemistry congress

Monday, 27-Aug 2012 | tuesday, 28-Aug 2012
s708
chem. Listy 106, s587–s1425 (2012)
life sciences
Biocatalysis session – iii
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KnowLedGe-BASed (re)deSiGn of
fLAvin-ContAininG BioCAtALyStS
M. frAAiJe 1
1 University of Groningen, Molecular Enzymology group,
Groningen, Netherlands
The catalytic potential of enzymes is more and more
appreciated by the industry and many industrial processes already
rely on these sophisticated biocatalysts. However, the number of
reactions catalyzed by enzymes is restricted as enzymes only have
evolved to catalyze reactions that are physiologically relevant.
Furthermore, enzymes have adapted to the cellular environment
in which they have to function. This excludes the existence of
enzymes that do not fit within the boundaries set by nature. It is a
great challenge to go beyond these natural boundaries and develop
methodologies to design ‘unnatural’ tailor-made enzymes. Ideally
it should become possible to (re)design enzymes to convert
pre-defined substrates. Such designer enzymes could theoretically
exhibit unsurpassed catalytic properties and, obviously, will be of
significant interest for industrial biotechnology.
Recent work in my research group has focused on discovery
of new oxidative enzymes and using them as template for enzyme
redesign studies. Examples of newly discovered and redesigned
redox enzymes, flavoprotein oxidases and Baeyer-Villiger
monooxygenases, will be presented. Mechanistic studies on these
biocatalysts have revealed new insights in how these enzymes
function. Using this knowledge, it has been possible to create
artificial enzymes that display catalytic properties not observed
in nature. Results on some recent enzyme redesign studies will be
highlighted in which new artificial enzymes were created by
cofactor redesign.
Keywords: Biocatalysis; Enzyme catalysis; Oxygenation;
Oxidation;
life science Multisymposium – i
4 th EucheMs chemistry congress
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CheMiCAL BioLoGy thAt ControLS dnA
StruCture And funCtion
h. SuGiyAMA 1 , 2
1 Department of Chemistry, Kyoto University, Japan
2 Institute for Integrated Cell-Materials Science (iCeMS), Kyoto
University, Japan
Fifty years after the discovery of the double-helical structure
of DNA, the complete sequence of the human genome has been
determined. Many diseases, including cancer, hereditary, and viral
diseases, can now be understood at the DNA sequence level.
Recently, it has been revealed that epigenetic modification plays
an important role in gene expression, which controls the gene
expression through DNA methylation and histone modification.
This is closely related to the cell reprogramming and
differentiation. We have been undertaking original research on the
molecular recognition of DNA by antitumor antibiotics, and the
analysis of atom-specific chemical reaction toward DNA with
these agents. By reconstituting such knowledge, various
functionalized sequence-specific DNA binders were synthesized
as an artificial genetic switch. [1] Furthermore we have
demonstrated to control the reactions with DNA methylase and
repair enzymes in a designed DNA nanostructure, DNA origami,
and analyzed the single reaction using high-speed atomic force
microscope (AFM). [2] Recent progress of regulation of the
epigenetic gene expression using designed molecules, and
elucidation the mechanism using single molecular imaging
technique will be discussed.
references:
1. a) Synthetic Small Molecules for Epigenetic Activation of
Pluripotency Genes In Mouse Embryonic Fibroblasts.
Pandian, G.N.; Shinohara, K.; Ohtsuki, A.; Nakano, Y.;
Masafumi, M.; Bando, T.; Nagase, H.; Yamada, Y.;
Watanabe, A.; Terada, N.; Sato, S.; Morinaga, H.;
Sugiyama, H. ChemBioChem, 2011, 12, 2822–2828.
b) A Synthetic Small Molecule for Rapid Induction of
Multiple Pluripotency Genes in Mouse Embryonic
Fibroblast. Ganesh Pandian, N.; Nakano, Y; Sato, S;
Morinaga, H; Bando, T; Nagase, H; Sugiyama, H.
Scientific Reports, In Press.
c) Programmable Genetic Switiches to Control
Transcrpitional machinery of Pluripotency. Ganesh
Pandian, N; Sugiyama, H. Biotechnol. J. 2012, 7,
798–809.
2. a) A DNA-Based Molecular Motor that can Navigate a
Network of Tracks. Wickham, S.F.J; Bath, J.; Katsuda,
Y.; Endo, M.; Hidaka, K.; Sugiyama, H.; Tuberfield,
A.J. Nature Nanotechnol., 2012, 7, 169–173.
b) Single-Molecule Analysis Using DNA
Origami. Rajendran, A.; Endo, M.; Sugiyama,
H. Angew. Chem. Int. Ed., 2012, 51, 874–890.
Keywords:
AUGUst 26–30, 2012, PrAGUE, cZEcH rEPUbLIc