Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.1.1.32 (
phosphoenolpyruvate carboxykinase
)
4,204
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Production of propionic acid by fermentation of propionibacteria has gained increasing attention in the past few years. However, biomanufacturing of propionic acid cannot compete with the current oxo-petrochemical synthesis process due to its well-established infrastructure, low oil prices and the high downstream purification costs of microbial production. Strain improvement to increase propionic acid yield is the best alternative to reduce downstream purification costs. The recent generation of genome-scale models for a number of
Propionibacterium
species facilitates the rational design of metabolic engineering strategies and provides a new opportunity to explore the metabolic potential of the Wood-Werkman cycle. Previous strategies for strain improvement have individually targeted acid tolerance, rate of propionate production or minimisation of by-products. Here we used the
P. freudenreichii
subsp
. shermanii
and the pan-
Propionibacterium
genome-scale metabolic models (GEMs) to simultaneously target these combined issues. This was achieved by focussing on strategies which yield higher energies and directly suppress acetate formation. Using
P. freudenreichii
subsp
. shermanii
, two strategies were assessed. The first tested the ability to manipulate the redox balance to favour propionate production by over-expressing the first two enzymes of the pentose-phosphate pathway (PPP), Zwf (glucose-6-phosphate 1-dehydrogenase) and Pgl (
6-phosphogluconolactonase
). Results showed a 4-fold increase in propionate to acetate ratio during the exponential growth phase. Secondly, the ability to enhance the energy yield from propionate production by over-expressing an ATP-dependent
phosphoenolpyruvate carboxykinase
(
PEPCK
) and sodium-pumping methylmalonyl-CoA decarboxylase (MMD) was tested, which extended the exponential growth phase. Together, these strategies demonstrate that
in silico
design strategies are predictive and can be used to reduce by-product formation in
Propionibacterium
. We also describe the benefit of carbon dioxide to propionibacteria growth, substrate conversion and propionate yield.
...
PMID:Genome-scale model guided design of
Propionibacterium
for enhanced propionic acid production. 2925 72
