초록
<P><B>Abstract</B></P> <P>A novel strategy to finely control a large metabolic flux by using a “metabolic transistor” approach was established. In this approach a small change in the level or availability of an essential component for the process is controlled by adding a competitive reaction that affects a precursor or an intermediate in its biosynthetic pathway. The change of the basal level of the essential component, considered as a base current in a transistor, has a large effect on the flux through the major pathway. In this way, the fine-tuning of a large flux can be accomplished. The “metabolic transistor” strategy was applied to control electron transfer chain function by manipulation of the quinone synthesis pathway in <I>Escherichia coli</I>. The achievement of a theoretical yield of lactate production under aerobic conditions via this strategy upon manipulation of the biosynthetic pathway of the key participant, ubiquinone-8 (Q8), in an <I>E. coli</I> strain provides an in vivo, genetically tunable means to control the activity of the electron transfer chain and manipulate the production of reduced products while limiting consumption of oxygen to a defined amount.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The “metabolic transistor” strategy was established in <I>E. coli</I>. </LI> <LI> Fine-tuning of a large metabolic flux can be achieved by this strategy. </LI> <LI> Control of electron transfer chain of <I>E. coli</I> can be achieved by this strategy. </LI> <LI> Control of the metabolic burn rate and CO<SUB>2</SUB> release of <I>E. coli</I> can be accomplished. </LI> <LI> Theoretical yield of lactate was produced under fully aerobic conditions. </LI> </UL> </P>