초록
<P><B>Background</B></P><P>3-hydroxypropionic acid (3-HP) is an important platform for the production of C3 chemicals, including acrylic acid, methyl acrylate, and acrylamide. Microbial production of 3-HP is mainly due to glycerol metabolism. In this study, in order to improve microbial 3-HP production, we applied a metabolic toggle switch for controlling the glycerol metabolism to redirect the excess metabolic flux of central metabolic pathway toward an exogenous 3-HP producing pathway in <I>Escherichia coli</I>.</P><P><B>Results</B></P><P>The metabolic toggle switch enables conditional repression of the expression of a target gene during the fermentation. We individually performed conditional repression of <I>glpK</I>, <I>tpiA</I>, and <I>gapA,</I> which are involved in glycerol metabolism. The conditional repression of <I>glpK</I> and <I>tpiA</I> was not effective for 3-HP production under our experimental conditions. However, <I>gapA</I> conditional repression contributed to improve 3-HP production (titer, 54.2 ± 1.5 mM; yield, 32.1 ± 1.3 %) compared with that for the wild type strain. Additional deletion of endogenous <I>yqhD</I>, which is responsible for the production of a major byproduct, 1,3-propandiol, further increased 3-HP production (titer, 67.3 ± 2.1 mM; yield, 51.5 ± 3.2 %). The titer and yield were 80 and 94 % higher than those of the wild type strain, respectively. The obtained 3-HP yield from glycerol is comparable with the highest yield ever reported for microbial 3-HP production using glycerol as a sole carbon source. The measurement of intracellular metabolites showed the metabolic toggle switch successfully controlled the metabolic flux.</P><P><B>Conclusion</B></P><P>The conditional repression of <I>gapA</I> by using the metabolic toggle switch combined with deletion of endogeneous <I>yqhD</I> increased 3-HP production approximately twofold from glycerol. This result indicates the metabolic toggle switch can be applied in various bio-production using diverse substrates.</P>