Ge Jiawei, Wang Ting, Yu Hongwei, Ye Lidan
Key Laboratory of Biomass Chemical Engineering (Education Ministry), College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, China.
Institute of Bioengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 310058, China.
Nat Commun. 2025 Jan 2;16(1):175. doi: 10.1038/s41467-024-55739-0.
Nylon 12 is valued for its exceptional properties and diverse industrial applications. Traditional chemical synthesis of nylon 12 faces significant technical challenges and environmental concerns, while bioproduction from plant-extracted decanoic acid (DDA) raises issues related to deforestation and biodiversity loss. Here, we show the development of an engineered Escherichia coli cell factory capable of biosynthesizing the nylon 12 monomer, ω-aminododecanoic acid (ω-AmDDA), from glucose. We enable de novo biosynthesis of ω-AmDDA by introducing a thioesterase specific to C12 acyl-ACP and a multi-enzyme cascade converting DDA to ω-AmDDA. Through modular pathway engineering, redesign and dimerization enhancement of the rate-limiting P450, reconstruction of redox and energy homeostasis, and enhancement of oxidative stress tolerance, we achieve a production level of 471.5 mg/L ω-AmDDA from glucose in shake flasks. This work paves the way for sustainable nylon 12 production and offers insights for bioproduction of other fatty acid-derived products.
尼龙12因其卓越的性能和多样的工业应用而备受重视。传统的尼龙12化学合成面临重大技术挑战和环境问题，而从植物提取的癸酸（DDA）进行生物生产则引发了与森林砍伐和生物多样性丧失相关的问题。在此，我们展示了一种经过工程改造的大肠杆菌细胞工厂的开发，该工厂能够从葡萄糖生物合成尼龙12单体ω-氨基十二烷酸（ω-AmDDA）。我们通过引入一种对C12酰基-ACP特异的硫酯酶和一个将DDA转化为ω-AmDDA的多酶级联反应，实现了ω-AmDDA的从头生物合成。通过模块化途径工程、限速P450的重新设计和二聚化增强、氧化还原和能量稳态的重建以及氧化应激耐受性的提高，我们在摇瓶中从葡萄糖实现了471.5 mg/L ω-AmDDA的生产水平。这项工作为可持续的尼龙12生产铺平了道路，并为其他脂肪酸衍生产品的生物生产提供了见解。
