Download 大學系所網管維運模式： 臺灣師大工教系經驗

共21頁，第1頁
Systems Biology Presentation
Modeling and Simulating the
Biological Pathway
- case study 第六組
NTHU
共21頁，第2頁
Outline
• Information gathering
– KEGG web service
– Ontology-based knowledge extraction
• Modeling environment
– Stoichiometric matrix
• Simulating environment
– Kinetics model
• Results and discussion
NTHU
共21頁，第3頁
Global agent Architecture
Pathway modeling agent
Model
the pathway
according to
the promoter
and
molecular
interactions
Extract
the
molecular
interactions
and
Chemical
coefficients
Quantitative Simulation agent
Bio-ontology
& thesauri
Literature extraction agent
According to
the
Quality of Service
and use’s goal
to make the
Biological plan
Measure the
chemical values
by calculating
the coefficients
and
pathway
structure
Workflow Planning agent
Information wrapper Agent
Information Gathering
Web service Matchmaker (Broker Agent)
Connect the service
Database (KEGG, NCBI, Micro-array)、Bioinformatics Toolkit
NTHU
共21頁，第4頁
Architecture
Kinetics
database
Get the kinetics coefficient
from the experiments
or literature
Biological
database
Get the gene name,
chemical compound and
its physical information
chemical
database
Get the chemical reaction
Pathway
database
Get the biological pathway
Dynamic model
Stoichiometric model
NTHU
共21頁，第5頁
Benefit
• Relational database system for managing
kinetic data, chemical structure, pathway,
chemical reaction
• Provide stoichiometric information and
parameters for kinetics equations to the
model
NTHU
共21頁，第6頁
Web service-KEGG
KEGG API provides valuable means for
accessing the KEGG system, such as for
searching and computing biochemical
pathways in cellular processes or analyzing
the universe of genes in the completely
sequenced genomes.
get_genes_by_pathway,
get_enzymes_by_pathway,
get_compounds_by_pathway,
get_reactions_by_pathway
….etc
The users can access the KEGG API server
by the SOAP technology over the HTTP
protocol. The SOAP server also comes with
the WSDL, which makes it easy to build a
client library for a specific computer language.
NTHU
共21頁，第7頁
Ontology-based knowledge extraction
• Concentration (mM), Volume (m),Flux
(mM/s),PH,…etc
• C-mol/min*L-cytosol
– where C-mol is a mol of carbon and L-cytosol
is a litre of cytosolic water
• Sentence:
– The pyruvate concentration that is required to
accommodate a flux of 0.48 C-mol/min*Lcytosol, is 8 mM.
NTHU
共21頁，第8頁
Glycolysis
NTHU
共21頁，第9頁
Enzyme Kinetics
One substrate, one product reversible Michaelis-Menten kinetics was
used to describe the enzymes PGI, PGM and ENO:
where a and p represent the concentrations of the corresponding
substrate and product, respectively. G is the mass-action ratio, p/a, Keq
is the equilibrium constant, peq/aeq. Ka and Kp are the MichaelisMenten constants for a and p.
Reversible Michaelis-Menten kinetics for two noncompeting substrateproduct couples was used for HK, GraPDH, PGK and PYK:
where a and b represent the concentrations of the substrates and
p and q the concentrations of the products.
NTHU
共21頁，第10頁
Example
NTHU
共21頁，第11頁
Results
NTHU
共21頁，第12頁
Results (II)
NTHU
共21頁，第13頁
Future work
• The combination of flux based static modeling
with dynamic modeling based on kinetic
equations
• The model can be initiated as a stoichiometric
model that is gradually converted into a dynamic
model by adding dynamic equations.
• Flux distribution analysis as a method for
calculating each flux in stoichiometric models.
• Substances at the boundary between dynamic
models and stoichiometric model are influenced
by both flux.
NTHU
共21頁，第14頁
Systems Biology Presentation
Biosynthesis of Ethanol
by E.coli
NTHU
共21頁，第15頁
Glycolysis
NTHU
共21頁，第16頁
Problem
NTHU
共21頁，第17頁
Pyruvate Decarboxylase
•
Reference
– Saccharomyces cerevisiae pyruvate
decarboxylase PDC1 has been isolated and
fused to the indicator gene Escherichia coli
lacZ.
– T7 RNA polymerase promoter phi 10, that a
cloned Saccharomyces cerevisiae pyruvate
decarboxylase gene ( pdc1) can be
expressed in Escherichia coli.
NTHU
共21頁，第18頁
Alcohol Dehydrogenase
• Only strain K-12 definitely have alcohol
dehydrogenase (adhP)
• alcohol dehydrogenase (EC 1.1.1.1)
NTHU
共21頁，第19頁
Escherichia coli strain KO11
• E. coli KO11 and three ethanol-resistant
mutants of this strain (LY01-LY03).
• Strain KO11 is an ethanol-producing
recombinant in which the
– Z. mobilis genes for ethanol production (pdc,
adhB)
– and the cat gene (acetyltransferase) have
been integrated into the E. coli B chromosom.
NTHU
共21頁，第20頁
Two strain used for this!
1. Strain K-12
•
•
definitely have alcohol dehydrogenase (adhP)
Saccharomyces cerevisiae pyruvate
decarboxylase (pdc1) recombinant
2. Escherichia coli strain KO11
•
Z. mobilis genes for ethanol production (pdc,
adhB) recombinant
NTHU
共21頁，第21頁
Reference
• Karp, P.D.; Riley, M.; Saier, M.; Paulsen, I.T.;
Collado-Vides, J.; Paley, S.; Pellegrini-Toole, A.;
Bonavides, C.; Gama-Castro, S. The Ecocyc
database. Nucleic Acids Res. 2002, 30,56-58
• Yomano, L.P.; York, S.W.; Ingram, L.O. Journal
of Industrial Microbiology & Biotechnology.
Isolation and characterization of ethanol-tolerant
mutants of Escherichia coli KO11 for fuel ethanol
production. 1998, 20, 132-138
NTHU