Nature communications · 2026
Towards an enzyme cascade synthesis of the bulk chemical acrylic acid.
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Zhao Haodong, Wang Chunying, Zhang Shiqing, Wang Qian, Chu Huanyu, Yang Jinying, Zhang Lei, Xu Zhanmei, Zhuo Bingzhao, Liu Cui, Mao Yufeng, Lu Lina, Zhang Xu, Zhao Huiru, Ma Yanhe, Sheng Xiang, Liu Yuwan, Jiang Huifeng
Аннотация
Acrylic acid is a bulk chemical predominantly produced via fossil-based processes. Here, we repurpose and engineer a thiamine diphosphate (ThDP)-dependent enzyme to catalyze direct H 2 PO 4 - elimination from dihydroxyacetone phosphate (DHAP) for acrylic acid synthesis. Quantum chemical calculations reveal the catalytic mechanism involving isomerization, enol-ThDP intermediate formation, H 2 PO 4 - elimination, and hydrolysis. Using an automated high-throughput screening platform, we perform directed evolution and obtain a 13.6-fold improved variant, designated acrylic acid synthase (AAS). We establish an enzymatic methanol-to-acrylic acid (MAAP) pathway, achieving a titer of 4.3 g L-1, a productivity of 268.9 mg L-1 h-1, and 99.5% conversion. This work establishes a high-efficiency biomanufacturing paradigm for bulk acrylic acid, and expands the catalytic repertoire of ThDP-dependent enzymes for sustainable one-carbon conversion.