Metabolic Engineering of Lactococcus lactis
Catherine
Lloyd
Auckland Bioengineering Institute, The University of Auckland
Model Status
This model runs in OpenCell and COR and the units are consistent throughout. The output is similar to the original model simulation, but differs for unknown reasons. The CellML model translation is based on the the original model code which is available online at the JWS website.
Model Structure
ABSTRACT: Everyone who has ever tried to radically change metabolic fluxes knows that it is often harder to determine which enzymes have to be modified than it is to actually implement these changes. In the more traditional genetic engineering approaches 'bottle-necks' are pinpointed using qualitative, intuitive approaches, but the alleviation of suspected 'rate-limiting' steps has not often been successful. Here the authors demonstrate that a model of pyruvate distribution in Lactococcus lactis based on enzyme kinetics in combination with metabolic control analysis clearly indicates the key control points in the flux to acetoin and diacetyl, important flavour compounds. The model presented here (available at http://jjj.biochem.sun.ac.za/wcfs.html) showed that the enzymes with the greatest effect on this flux resided outside the acetolactate synthase branch itself. Experiments confirmed the predictions of the model, i.e. knocking out lactate dehydrogenase and overexpressing NADH oxidase increased the flux through the acetolactate synthase branch from 0 to 75% of measured product formation rates.
Metabolic engineering of lactic acid bacteria, the combined approach: kinetic modelling, metabolic control and experimental analysis, Marcel H.N. Hoefnagel, Marjo J.C. Starrenburg, Dirk E. Martens, Jeroen Hugenholtz, Michiel Kleerebezem, Iris I. Van Swam, Roger Bongers, Hans V. Westerhoff, and Jacky L. Snoep, 2002, Microbiology, 148, 1003-1013. PubMed ID: 11932446
reaction diagram
A schematic diagram of the reactions included in the model to describe the distribution of carbon from pyruvate in L. lactis.
PYR
pyruvate
ACP
acetyl phosphate
ACAL
acetaldehyde
ACLAC
acetolactate
ACET
acetoin
ATP
adenosine triphosphate
ADP
adenosine diphosphate
NADH
nicotinamide adenine dinucleotide
NAD
positive nicotinamide adenine dinucleotide
ACCOA
acetyl coenzyme A
COA
coenzyme A
AC
acetate
BUT
2,3-butanediol
ETOH
ethanol
GLC
glucose
LAC
lactate
O
oxygen
P
inorganic phosphate
Hoefnagel et al's 2002 mathematical model of pyruvate distribution in
lactic acid bacteria.
The University of Auckland, Auckland Bioengineering Institute
Jacky
Snoep
L
Marcel
Hoefnagel
H
N
Catherine Lloyd
keyword
metabolic control
pyruvate
metabolism
Michiel
Kleerebezem
2002-04
This is the CellML description of Hoefnagel et al's 2002 mathematical
model of pyruvate distribution in lactic acid bacteria.
Hans
Westerhoff
V
Jeroen
Hugenholtz
Dirk
Martens
E
Marjo
Starrenburg
C
J
Catherine
Lloyd
May
Microbiology
Roger
Bongers
c.lloyd@auckland.ac.nz
Iris
Van Swam
I
11932446
2003-08-18
The University of Auckland
Auckland Bioengineering Institute
Metabolic engineering of lactic acid bacteria, the combined
approach: kinetic modelling, metabolic control and experimental
analysis
148
1003
1013