Hyperproduction of 3-hydroxypropionate by Halomonas bluephagenesis.
Hyperproduction of 3-hydroxypropionate by Halomonas bluephagenesis.
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蓝色盐单胞菌过量产生 3-羟基丙酸
DOI：
10.1038/s41467-021-21632-3
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发表时间：
2021-03-08
影响因子：
16.6
通讯作者：
Chen GQ
中科院分区：
文献类型：
--
作者：
Jiang XR;Yan X;Yu LP;Liu XY;Chen GQ
3-羟基丙酸(3HP)是一种重要的三碳(C3)化合物，被指定为工业生产急需改进的顶级平台化学品之一。由于能够在开放、无菌和连续的过程中生长，Halomonas Bluephagenesis显示出作为各种化学品竞争生物生产底盘的潜力。在此，我们报道了利用发酵法生产3HP及其共聚物poly(3-hydroxybutyrate-co-3-hydroxypropionate)(P3HB3HP)的策略。转录组分析揭示了其3HP的降解和合成途径，涉及1，3-丙二醇的内源合成酶。结合乙醛脱氢酶(AldDHb)的优化表达，构建了一株在平衡氧化还原状态下缺失3HP降解途径并在基因组上过表达乙醇脱氢酶(ADHP)的蓝色发育菌，构建了依赖1，3-丙二醇的3HP生物合成增强途径，获得了产量为0.93g g g−1 1，3-丙二醇和2.4 g L−1 h−1的3HP产量和生产能力。此外，该菌株还能在干细胞团中积累60%的聚(3-羟基丁酸酯-32-45%3-羟基丙酸)，表明该菌株是高产3HP和P3HB3HP的合适底盘。3-羟基丙酸(3HP)是一种重要的平台化合物。在这里，作者通过删除新发现的降解途径和平衡氧化还原状态来改造嗜盐单胞菌的蓝头形成，从而在开放和无菌条件下实现3HP及其共聚物的高水平生产。
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 (AldDHb), 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−1 of 3HP with a yield and productivity of 0.93 g g−1 1,3-propanediol and 2.4 g L−1 h−1, 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-Hydroxypropionic acid (3HP) is an important platform chemical. Here, the authors engineer Halomonas bluephagenesis by deleting newly identified degradation pathway and balancing redox state to achieve high level production of 3HP and its copolymer under open and unsterile conditions.
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