Transcript Find the metabolic pathways involved in the synthesis of the Lysine

Introductions to Lysine in E.coli
Metabolism Pathways.
Group 9
張智宏 楊翊文 王翔昱
2005.1.14
Outline
 Describe the usage of Lysine.

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Process
Find the metabolic pathways involved in the
synthesis of the Lysine .
Find the enzymes and genes involved in these
pathway reactions .
Is E. Coli suitable for biosynthesis of Lysine ?
Introductions to Lysin
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Symbol : lys k , 離胺酸
Molecular formula : C6H14N2O2
Molecular weight : 146.19
Isoelectric point (pH) : 9.59
pKa values : 2.20, 8.90, 10.28
CAS Registry Number : 56-87-1
Type : lonic
Other Forms
L-lysine acetylsalicylate (LAS)
Lysine clonixinate (LC)
L-lysine monohydrochlorine (LMH)
Query interface ...
Introductions to Lysine
H2N-(CH2)4-CH(NH2)-COOH
3D Molecular Model
Lysine under the microscope
Introductions to Lysine
Discovered in 1989 .
Lysine is incorporated into proteins at the rate of 7 percent on a molar
basis compared to the other amino acids.
The side chain of Lysine has three methylene groups, so that even though
the terminal amino group will be charged under physiological conditions,
the side chain does have significant hydrophobic character.
Lysine is an essential amino acid that you must get from food because
your body cannot make enough of it.
Lysine helps your body process fatty acids, and it is particularly
important for proper growth.
Lysine helps your body absorb calcium, and it plays an important role in
the formation of collagen, a substance important to your bones and tissues.
Medical Information of Lysine
Lysine is used to treat herpes infections caused by both herpes simplex
and herpes zoster viruses. Taking lysine supplements can speed your
recovery time and reduce chances of reinfection.
Some studies have found lysine helpful in treating cardiovascular disease,
osteoporosis, asthma, migraine, nasal polyps, and postepisiotomy pain.
If you get too little lysine in your diet, your body may develop a poor
nitrogen balance, and you may ultimately develop kidney stones.
Signs of getting too little lysine include fatigue, nausea, dizziness, appetite
loss, emotional agitation, bloodshot eyes, decreased immunity, slow
growth, anemia, enzyme deterioration, reproductive disorders,
pneumonia, and acidosis (a pH imbalance in the body).
The most concentrated sources of lysine are torula yeast, dried and salted
cod, Parmesan cheese, pork loin (excluding fat), dried and frozen tofu.
Outline

Describe the usage of Lysine.
 Process



Find the metabolic pathways involved in the
synthesis of the Lysine .
Find the enzymes and genes involved in these
pathway reactions .
Is E. Coli suitable for biosynthesis of Lysine ?
Process , What we have done
http://www.genome.jp/kegg/
Click “ Ligand ” to enter query interface
Query “Lysine” with “ name” function
Process , What we have done
Select the entry that match our desire: entry C00047
We are interested in
Lysine biosynthesis,
select the path
map00300
Process , What we have done
Show the enzymes exist in E.Coli with green color
Outline


Describe the usage of Lysine.
Process
 Find the metabolic pathways involved in
the synthesis of the Lysine .


Find the enzymes and genes involved in these
pathway reactions .
Is E. Coli suitable for biosynthesis of Lysine ?
Find the metabolic pathways involved in the
synthesis of the Lysine .
Lysine Biosynthesis
(Alanine and Aspartate Metabolism)  L-Asparate  2.7.2.4 
L-4-Aspartyl Phosphate  1.2.1.11  L-Aspartate 4-Semialdehyde
4.2.1.52  2,3-Dihydrodipicolinate  1.3.1.26 
2,3,4,5,-Tetrahydro-dipicolinate  2.3.1.117 
N-Succinyl-2-amino-6-oxopimelate  2.6.1.17 
N-Succinyl-L-2,6-diaminopimelate
 3.5.1.18  2,6-diominopimelate  5.1.1.7  meso-2,6-Diaminopimelate
 4.1.1.20  L-Lysine
Alanine and Aspartate Metabolism
(Glycosis)  Pyruvate Acetyl-Coa
 Cirate 2-Oxoglutarate
Succinate  Fumarate
 4.3.1.1 L-Aspartate (Lysine Biosynthesis)
D-Glucose  2.7.1.69
α-D-Glucose-6p  5.3.1.9
β-D-Fructose-6p
2.7.1.11
β-D-Fructose-1,6p2
4.1.2.13
Glyceraldehyde-3p
1.2.1.12
Glycerate-1,3p2
3.6.1.7 (2.7.2.3)
Glycerate-3p
5.4.2.1
Glycerate-2p
4.2.1.11
Phosphoenolpyruvate
2.7.1.40
(Alanine and Aspartate
Metabolism)
Glycolysis
Outline



Describe the usage of Lysine.
Process
Find the metabolic pathways involved in the
synthesis of the Lysine .
 Find the enzymes and genes involved in
these pathway reactions .

Is E. Coli suitable for biosynthesis of Lysine ?
Lysine Biosynthesis Pathway
Entry EC 2.3.1.117
ECO: b0166(dapD)
Entry EC 2.6.1.17
ECO: b2379(yfdZ)
Entry EC 3.5.1.18
ECO: b2472(dapE)
Entry EC 5.1.1.7
ECO: b3809(dapF)
Entry EC 4.1.1.20
ECO: b2838(lysA)
Entry EC 2.7.2.4
ECO: b0002(thrA)
b3940(metL)
b4024(lysC)
Entry EC 1.2.1.11
ECO: b3433(asd)
Entry EC 4.2.1.52
ECO: b2478(dapA)
Entry EC 1.3.1.26
ECO: b0031(dapB)
Alanine and Aspartate Metabolism Pathway
Entry EC 4.3.1.1
ECO: b4139(aspA)
Name : aspartate ammonia-lyase
aspartase
fumaric aminase
L-aspartase
Definition : aspartate ammonia-lyase (aspartase)
Glycosis Pathway
Entry EC 2.7.1.69
ECO: b0129(yadI)
b0679(nagE)
b0731(hrsA)
b1101(ptsG)
b1621(malX)
b1736(celC)
b1738(celA) …..
Entry EC 5.3.1.9
ECO: b4025(pgi)
Entry EC 2.7.1.11
ECO: b1723(pfkB) b3916(pfkA)
Entry EC 4.1.2.13
ECO: b2097(dhnA) b2925(fba)
Entry EC 1.2.1.12
ECO: b1416(gapC_2)
b1417(gapC)
b1779(gapA)
Entry EC 2.7.2.3
ECO: b2926(pgk)
Entry EC 5.4.2.1
ECO: b0755(gpmA) b3612(yibO)
Entry EC 4.2.1.11
ECO: b2779(eno)
Entry EC 2.7.1.40
ECO: b1676(pykF) b1854(pykA)
Outline




Describe the usage of Lysine.
Process
Find the metabolic pathways involved in the
synthesis of the Lysine .
Find the enzymes and genes involved in these
pathway reactions .
 Is E. Coli suitable for biosynthesis of
Lysine ?
Is E. Coli suitable for
biosynthesis of Lysine ?
• Methylotrophs, microorganisms that use reduced onecarbon compounds, are diverse and ubiquitous. Even
though many methylotrophs have been described, only a
few are gram positive. The industrial advantages of using
methanol as a substrate for large-scale production of
fermentation products have been outlined by other groups.
Methanol is relatively inexpensive, prices are relatively
stable, production exceeds demand, and it is easily stored
and transported. In addition, methanol is available in pure
form, it is highly soluable in water, methanol solutions are
not explosive, and residual methanol can be easily removed
from products after fermentation is completed. Bacillus
species have been used extensively in industrial
fermentation processes
Second Part
Using Linear program
• Our goal is to maximize the quantity of
Lysine by using Linear program.
• 1129 biochemical reactions and 1177
compounds of E.Coli are parsed to
obtain the coefficient matrix
• In the solution X each xi denotes the
percentage of each reaction.
Resource
• 1129 biochemical reactions and 1177
compounds of E.Coli are parsed to
obtain the coefficient matrix
• We fail to figure out the result if all
biochemical reactions and
compounds are considered.
Alternative resource
But it works when we ignore
all reactions and compounds.
The relationship of
compounds related to Lysine
is represented as follow :
max C00047(lysine)
subject to
R1=100
R10-R11=0
R1-R2=0
R11-R12=0
R2-R3=0
R12-R13-R17=0
R3-R4=0
R13-R14=0
R4-R5=0
R14-R15=0
R5-R6=0
R16+R28-R29=0
R6-R7=0
R17-R18=0
R7-R8=0
R18-R19=0
R8-R9-R16=0
R19-R20=0
R9-R10=0
R20-R21=0
R21-R22=0
R34-R35=0
R22-R23=0
R35-R36=0
R23-R24=0
R36-R37=0
R24-R25=0
R37-R38=0
R25-R26=0
R40-R41=0
R26-R27=0
R39-R40-R42=0
R27-R28=0
R42-R43=0
R29-R30=0
R43-R44=0
R30-R31=0
-100<=Ri<=100
R31-R39-R32=0
R32-R33=0
R33-R34=0
Result
• Input data: E.coli reactions (KEGG)
• Result
Methionine=0, Threonine=0, Lysine=47.5
Describe the usage of Lysine.
Find the metabolic pathways involved in
the synthesis of the following compound .
Thank You !
Find the enzymes and genes involved in
these pathway reactions .
Is E. Coli suitable for biosynthesis of
Lysine ?
Group9, 2004.11.19