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

GMP

IMP

AMP

HGPRT

APRT

The future

Disease phenotype treatmentDrug design & developmentProtein 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

Contr

ol Pps

Pps

* Pps

#

-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?!