초록
<P><B>Significance</B></P><P>Production of industrial compounds by using engineered microorganisms is a robust method to reduce our reliance on nonrenewable petroleum resources and increase the utility of renewable resources, such as lignocellulose. Because there are major limitations for engineering a single microbial cell to achieve high-yield production, we developed microbial coculture systems consisting of two different microbial cell types to use sugar mixtures that can be derived from lignocellulose efficiently. We demonstrate that this approach is successful for achieving high-level production of two important value-added molecules, <I>cis</I>,<I>cis</I>-muconic acid and 4-hydroxybenzoic acid. This accomplishment establishes a previously unidentified technology for advancing future research in metabolic engineering and synthetic biology.</P><P>Engineering microbial consortia to express complex biosynthetic pathways efficiently for the production of valuable compounds is a promising approach for metabolic engineering and synthetic biology. Here, we report the design, optimization, and scale-up of an <I>Escherichia coli</I>-<I>E. coli</I> coculture that successfully overcomes fundamental microbial production limitations, such as high-level intermediate secretion and low-efficiency sugar mixture utilization. For the production of the important chemical <I>cis</I>,<I>cis</I>-muconic acid, we show that the coculture approach achieves a production yield of 0.35 g/g from a glucose/xylose mixture, which is significantly higher than reported in previous reports. By efficiently producing another compound, 4-hydroxybenzoic acid, we also demonstrate that the approach is generally applicable for biosynthesis of other important industrial products.</P>