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Lecture 25
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Drug therapy
THF metabolism inhibitors would have strongest effect on:
A. Stem cells
B. Cancer cells
C. All cells
D. All dividing cells
E. No cells
Purines  Uric acid
Pyrimidines  MeMalonyl semialdehyde
Salvage pathways
APRT
GMP
HGPRT
IMP
AMP
The future
Disease phenotype  treatment
Drug design & development
Protein engineering
Industrial applications
Diagnostics
Metabolic engineering
Engineer a whole pathway?
Large scale production?
Biosynthesis:
- Fuel
- Nutraceuticals
What else?!?!!
Example of metabolic engineering
Patnaik, R. and Liao, J. (1994). "Engineering of Escherichia coli central metabolism for aromatic
metabolite production with near theoretical yield". Appl. Environ. Microbiol. 60(11):3903-3908
Example of metabolic engineering
Patnaik, R. and Liao, J. (1994). "Engineering of Escherichia coli central metabolism for aromatic
metabolite production with near theoretical yield". Appl. Environ. Microbiol. 60(11):3903-3908
Example of metabolic engineering
Patnaik, R. and Liao, J. (1994). "Engineering of Escherichia coli central metabolism for aromatic
metabolite production with near theoretical yield". Appl. Environ. Microbiol. 60(11):3903-3908
-Omics = Metabolomics!
ENTIRE collection of metabolites!
“Metabolome”
Metabolome & drugs
Kaddurah-Daouk, Rima, Bruce S. Kristal, and Richard M. Weinshilboum. "Metabolomics: a global
biochemical approach to drug response and disease." Annu. Rev. Pharmacol. Toxicol. 48 (2008): 653-683.
Discovering diagnostic markers
Kenny, Louise C., et al. "Novel biomarkers for pre-eclampsia detected using metabolomics and machine learning." Metabolomics 1.3 (2005): 227-234.
Differentiating disease conditions
Kaddurah-Daouk, Rima, Bruce S. Kristal, and Richard M. Weinshilboum. "Metabolomics: a global
biochemical approach to drug response and disease." Annu. Rev. Pharmacol. Toxicol. 48 (2008): 653-683.
The Human Metabolome project
Synthetic biology – “creating” life…
“Build” a genome from scratch?
What is “minimal” genome?
…and beyond!
Protein + metabolic engineering
Any compound, any time!
“Download” vaccine to personal biofactory?!