Limitations
in
Metabolic
Engineering
Due
to
Network
Rigidity -
During metabolic engineering involving primary metabolism (e.g. glycolysis, TCA cycle and pentose phosphate pathway, etc.), the carbon flux distributions at key branch points (called 'nodes') is often radically redirected from the flux distributions that are normally associated with balanced growth.
Such flux alterations are often directly opposed by mechanisms that have evolved to maintain original flux distributions for optimal growth. This opposition to flux alterations at key branch points or nodes is often described as 'metabolic rigidity' or 'nodal rigidity'. There are relatively few examples where this nodal rigidity has been overcome through genetic manipulations leading to successful flux alterations.



