Department of Microbiology, Army Medical University, Chongqing, China.
School of Life Sciences, Tsinghua University, Beijing, China.
Nat Commun. 2021 Mar 8;12(1):1513. doi: 10.1038/s41467-021-21632-3.
3-Hydroxypropionic acid (3HP), an important three carbon (C3) chemical, is designated as one of the top platform chemicals with an urgent need for improved industrial production. Halomonas bluephagenesis shows the potential as a chassis for competitive bioproduction of various chemicals due to its ability to grow under an open, unsterile and continuous process. Here, we report the strategy for producing 3HP and its copolymer poly(3-hydroxybutyrate-co-3-hydroxypropionate) (P3HB3HP) by the development of H. bluephagenesis. The transcriptome analysis reveals its 3HP degradation and synthesis pathways involving endogenous synthetic enzymes from 1,3-propanediol. Combing the optimized expression of aldehyde dehydrogenase (AldD), an engineered H. bluephagenesis strain of whose 3HP degradation pathway is deleted and that overexpresses alcohol dehydrogenases (AdhP) on its genome under a balanced redox state, is constructed with an enhanced 1.3-propanediol-dependent 3HP biosynthetic pathway to produce 154 g L of 3HP with a yield and productivity of 0.93 g g 1,3-propanediol and 2.4 g L h, respectively. Moreover, the strain could also accumulate 60% poly(3-hydroxybutyrate-co-32-45% 3-hydroxypropionate) in the dry cell mass, demonstrating to be a suitable chassis for hyperproduction of 3HP and P3HB3HP.
3-羟基丙酸（3HP）是一种重要的三碳（C3）化学品，被指定为急需提高工业生产的顶级平台化学品之一。盐单胞菌蓝藻具有在开放、非无菌和连续过程中生长的能力，因此有望成为各种化学品竞争生物生产的底盘。在这里，我们报告了通过开发盐单胞菌蓝藻生产 3HP 和其共聚物聚（3-羟基丁酸-co-3-羟基丙酸）（P3HB3HP）的策略。转录组分析揭示了其 3HP 降解和合成途径，涉及来自 1,3-丙二醇的内源性合成酶。通过优化醛脱氢酶（AldD）的表达，构建了一个工程化的盐单胞菌蓝藻菌株，该菌株缺失了 3HP 降解途径，并在其基因组上过表达了醇脱氢酶（AdhP），在平衡的氧化还原状态下，该菌株构建了一个增强的 1,3-丙二醇依赖的 3HP 生物合成途径，以生产 154 g L 的 3HP，产率和生产效率分别为 0.93 g g 1,3-丙二醇和 2.4 g L h。此外，该菌株还可以在干细胞质量中积累 60%的聚（3-羟基丁酸-co-32-45% 3-羟基丙酸），表明其是 3HP 和 P3HB3HP 超生产的合适底盘。
