1. Essence of Metabolic Engineering
Substrate
What is metabolic engineering?
Some product is desired
A microorganism is found to produce the product in its metabolic cycles
The "natural" yield is slow or the condition of production is not suitable for industrial scale production
Genetic changes or environmental controls are used to improve the production
But how and why?
Desired products

2. Genes, enzymes and metabolites
Substrate
Metabolites
Molecular
Biology
Desired products
Engineering analysis

3. To increase the low yield of product Y in wild type cell, enzyme E3 is
over-expressed. However, due to network interactions, this has minimal
effect on the rates of product X and Y accumulations.

4. Contents Stoichiometry and mass balance Thermodynamics and Kinetics
Metabolic flux analysis
Metabolic Control analysis
Network Regulation

5. Knowledge pre-requisite
Basic physics and chemistry
Conservation of mass
Thermodynamics of Chemical Reaction
Chemical Reaction Kinetics
Linear algebra

6. Reading list Textbook Review papers
Metabolic Engineering - Principles and Methodology
G.N. Stephanopoulos, A.A. Aristidou and J. Nielson, AP 1998
Review papers
Metabolic engineering: Perspective of a chemical engineer
G. Stephanopooulos, AIChE J., v.48(5), p , 2002
A perspective of metabolic engineering strategies: moving up the systems hierarchy
T. Bulter, J.T. Bernstein, & J.C. Liao, Biotechnology and Bioengineering, v.84(7), p , 2003
How will bioinformatics influence metabolic engineering?
J.S. Edwards & B.O. Palson, Biotechnology and Bioengineering, v.58, p , 1998

7. Technical (To be appended)
Data reconciliation and parameter estimation in flux-balance analysis
A.U. Raghunathan, J. R. Perez-Correa & L.T. Bieger Biotechnology and Bioengineering, v. 84(6), p , 2003
Combining pathway analysis with flux balance analysis for the comprehensive study of metabolic systems
C.H. Schilling, J.S. Edwards, D. Letscher and B.O. Palsson, Biotechnology and Bioengineering v.71, p
Theory for the Systemic Definition of Metabolic Pathways and their use in Interpreting Metabolic Function from a Pathway-Oriented Perspective
C.H. Schilling, J.S. Edwards, D. Letscher and B.O. Palsson, J. Theoretical Biology, v.203, p , 2000
Optimization of regulatory architectures in metabolic reaction networks
V.C. Hatzimanikatis, C. A. Floudas & J.E. Bailey Biotechnology and Bioengineering, v.52(4),, p , 1996
Determination of Flux Control Coefficients from Transient Metabolite Concentrations
J. Delagado and J. C. Liao, Biochem. J., v. 282, , 1992