초록
<P><B>Abstract</B></P> <P>3-Hydroxypropionic acid (3-HP) is a promising platform chemical which can be used for the production of various value-added chemicals. In this study,<I>Corynebacterium glutamicum</I> was metabolically engineered to efficiently produce 3-HP from glucose and xylose via the glycerol pathway. A functional 3-HP synthesis pathway was engineered through a combination of genes involved in glycerol synthesis (fusion of <I>gpd</I> and <I>gpp</I> from <I>Saccharomyces cerevisiae</I>) and 3-HP production (<I>pduCDEGH</I> from <I>Klebsiella pneumoniae</I> and aldehyde dehydrogenases from various resources). High 3-HP yield was achieved by screening of active aldehyde dehydrogenases and by minimizing byproduct synthesis (<I>gapA</I> <SUP>A1G</SUP>Δ<I>ldhA</I>Δ<I>pta-ackA</I>Δ<I>poxB</I>Δ<I>glpK</I>). Substitution of phosphoenolpyruvate-dependent glucose uptake system (PTS) by inositol permeases (<I>iolT1</I>) and glucokinase (<I>glk</I>) further increased 3-HP production to 38.6g/L, with the yield of 0.48g/g glucose. To broaden its substrate spectrum, the engineered strain was modified to incorporate the pentose transport gene <I>araE</I> and xylose catabolic gene <I>xylAB</I>, allowing for the simultaneous utilization of glucose and xylose. Combination of these genetic manipulations resulted in an engineered <I>C. glutamicum</I> strain capable of producing 62.6g/L 3-HP at a yield of 0.51g/g glucose in fed-batch fermentation. To the best of our knowledge, this is the highest titer and yield of 3-HP from sugar. This is also the first report for the production of 3-HP from xylose, opening the way toward 3-HP production from abundant lignocellulosic feedstocks.</P> <P><B>Highlights</B></P> <P> <UL> <LI> <I>Corynebacterium glutamicum</I> was engineered for the first time to produce 3-hydroxypropionic acid (3-HP) from glucose via glycerol pathway. </LI> <LI> 62.6g/L of 3-HP was produced from glucose at a yield of 0.51g/g, the highest titer and yield of 3-HP from sugar reported to date. </LI> <LI> Downregulation of glyceraldehyde 3-phosphate dehydrogenase and employment of the non-PTS glucose-uptake system are important for increasing the yield of 3-HP. </LI> <LI> 3-HP overproduction by simultaneous utilization of glucose and xylose was achieved. </LI> </UL> </P>