초록
<P><B>ABSTRACT</B></P><P>3‐Hydroxypropionic acid (3‐HP) can be produced in microorganisms as a versatile platform chemical. However, owing to the toxicity of the intermediate product 3‐hydroxypropionaldehyde (3‐HPA), the minimization of 3‐HPA accumulation is critical for enhancing the productivity of 3‐HP. In this study, we identified a novel aldehyde dehydrogenase, GabD4 from <I>Cupriavidus necator</I>, and found that it possessed the highest enzyme activity toward 3‐HPA reported to date. To augment the activity of GabD4, several variants were obtained by site‐directed and saturation mutagenesis based on homology modeling. <I>Escherichia coli</I> transformed with the mutant GabD4_E209Q/E269Q showed the highest enzyme activity, which was 1.4‐fold higher than that of wild type GabD4, and produced up to 71.9 g L<SUP>−1</SUP> of 3‐HP with a productivity of 1.8 g L<SUP>−1</SUP> h<SUP>−1</SUP>. To the best of our knowledge, these are the highest 3‐HP titer and productivity values among those reported in the literature. Additionally, our study demonstrates that GabD4 can be a key enzyme for the development of industrial 3‐HP‐producing microbial strains, and provides further insight into the mechanism of aldehyde dehydrogenase activity. Biotechnol. Bioeng. 2015;112: 356–364. © 2014 Wiley Periodicals, Inc.</P>