초록
<P>3-Hydroxypropionic acid (3-HP) is an important platform chemical proposed by the United States Department of Energy. 3-HP can be converted to a series of bulk chemicals. Biological production of 3-HP has made great progress in recent years. However, low yield of 3-HP restricts its commercialization. In this study, systematic optimization was conducted towards high-yield production of 3-HP in <I>Klebsiella pneumoniae</I>. We first investigated appropriate promoters for the key enzyme (aldehyde dehydrogenase, ALDH) in 3-HP biosynthesis, and found that IPTG-inducible <I>tac</I> promoter enabled overexpression of an endogenous ALDH (PuuC) in <I>K. pneumoniae</I>. We optimized the metabolic flux and found that blocking the synthesis of lactic acid and acetic acid significantly increased the production of 3-HP. Additionally, fermentation conditions were optimized and scaled-up cultivation were investigated. The highest 3-HP titer was observed at 83.8 g/L with a high conversion ratio of 54% on substrate glycerol. Furthermore, a flux distribution model of glycerol metabolism in <I>K. pneumoniae</I> was proposed based on <I>in silico</I> analysis. To our knowledge, this is the highest 3-HP production in <I>K. pneumoniae</I>. This work has significantly advanced biological production of 3-HP from renewable carbon sources.</P>