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通过构建协调的双重生物合成途径,从甲醇中工程化生产高产量的脂肪醇。

Engineering high production of fatty alcohols from methanol by constructing coordinated dual biosynthetic pathways.

机构信息

Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; University of Chinese Academy of Sciences, Beijing 100049, China.

Division of Biotechnology, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.

出版信息

Bioresour Technol. 2024 Nov;412:131396. doi: 10.1016/j.biortech.2024.131396. Epub 2024 Aug 30.

DOI:10.1016/j.biortech.2024.131396
PMID:39216706
Abstract

Microbial cell factories provide an efficient approach for the green manufacturing of chemicals. However, the excessive use of sugars increases the potential risk of food crisis. Methanol, an abundant feedstock, holds promise in facilitating low-carbon production processes. However, the current methanol bioconversion is hindered by limited regulatory strategies and relatively low conversion efficiency. Here, a yeast biocatalyst was extensively engineered for efficient biosynthesis of fatty alcohols through reinforcement of precursor supply and methanol assimilation in Pichia pastoris. Furthermore, the dual cytoplasmic and peroxisomal biosynthetic pathways were constructed by mating and exhibited robust production of 5.6 g/L fatty alcohols by using methanol as the sole carbon source. This study provides a heterozygous diploid P. pastoris strain with dual cytoplasmic and peroxisomal biosynthetic pathways, which achieved the highest fatty alcohol production from one-carbon feedstocks to date.

摘要

微生物细胞工厂为化学品的绿色制造提供了一种有效的方法。然而,糖的过度使用增加了引发食物危机的潜在风险。甲醇作为一种丰富的原料,有望促进低碳生产过程。然而,目前甲醇的生物转化受到有限的调控策略和相对较低的转化效率的限制。在这里,通过强化酿酒酵母中前体供应和甲醇同化作用,对酵母生物催化剂进行了广泛的工程改造,以实现脂肪酸醇的高效生物合成。此外,通过交配构建了双细胞质和过氧化物酶体生物合成途径,并以甲醇为唯一碳源,表现出 5.6g/L 脂肪酸醇的强劲生产能力。本研究提供了一株具有双细胞质和过氧化物酶体生物合成途径的杂合二倍体巴斯德毕赤酵母菌株,它实现了迄今为止从一碳原料生产脂肪酸醇的最高产量。

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Bioresour Technol. 2024 Nov;412:131396. doi: 10.1016/j.biortech.2024.131396. Epub 2024 Aug 30.
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