Lignin valorization to bioplastics with an aromatic hub metabolite-based autoregulation system

Yiquan Zhao, Le Xue, Zhiyi Huang, Zixian Lei, Shiyu Xie, Zhenzhen Cai, Xinran Rao, Ze Zheng, Ning Xiao, Xiaoyu Zhang, Fuying Ma, Hongbo Yu and Shangxian Xie ()
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Yiquan Zhao: Huazhong University of Science and Technology
Le Xue: Huazhong University of Science and Technology
Zhiyi Huang: Huazhong University of Science and Technology
Zixian Lei: Huazhong University of Science and Technology
Shiyu Xie: Huazhong University of Science and Technology
Zhenzhen Cai: Huazhong University of Science and Technology
Xinran Rao: Huazhong University of Science and Technology
Ze Zheng: Huazhong University of Science and Technology
Ning Xiao: Guangxi Academy of Sciences
Xiaoyu Zhang: Huazhong University of Science and Technology
Fuying Ma: Huazhong University of Science and Technology
Hongbo Yu: Huazhong University of Science and Technology
Shangxian Xie: Huazhong University of Science and Technology

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: Abstract Exploring microorganisms with downstream synthetic advantages in lignin valorization is an effective strategy to increase target product diversity and yield. This study ingeniously engineers the non-lignin-degrading bacterium Ralstonia eutropha H16 (also known as Cupriavidus necator H16) to convert lignin, a typically underutilized by-product of biorefinery, into valuable bioplastic polyhydroxybutyrate (PHB). The aromatic metabolism capacities of R. eutropha H16 for different lignin-derived aromatics (LDAs) are systematically characterized and complemented by integrating robust functional modules including O-demethylation, aromatic aldehyde metabolism and the mitigation of by-product inhibition. A pivotal discovery is the regulatory element PcaQ, which is highly responsive to the aromatic hub metabolite protocatechuic acid during lignin degradation. Based on the computer-aided design of PcaQ, we develop a hub metabolite-based autoregulation (HMA) system. This system can control the functional genes expression in response to heterologous LDAs and enhance metabolism efficiency. Multi-module genome integration and directed evolution further fortify the strain’s stability and lignin conversion capacities, leading to PHB production titer of 2.38 g/L using heterologous LDAs as sole carbon source. This work not only marks a leap in bioplastic production from lignin components but also provides a strategy to redesign the non-LDAs-degrading microbes for efficient lignin valorization.

Date: 2024
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DOI: 10.1038/s41467-024-53609-3

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