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

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...

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Main Authors: Yiquan Zhao, Le Xue, Zhiyi Huang, Zixian Lei, Shiyu Xie, Zhenzhen Cai, Xinran Rao, Ze Zheng, Ning Xiao, Xiaoyu Zhang, Fuying Ma, Hongbo Yu, Shangxian Xie
Format: Article
Language:English
Published: Nature Portfolio 2024-10-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-53609-3
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author Yiquan Zhao
Le Xue
Zhiyi Huang
Zixian Lei
Shiyu Xie
Zhenzhen Cai
Xinran Rao
Ze Zheng
Ning Xiao
Xiaoyu Zhang
Fuying Ma
Hongbo Yu
Shangxian Xie
author_facet Yiquan Zhao
Le Xue
Zhiyi Huang
Zixian Lei
Shiyu Xie
Zhenzhen Cai
Xinran Rao
Ze Zheng
Ning Xiao
Xiaoyu Zhang
Fuying Ma
Hongbo Yu
Shangxian Xie
author_sort Yiquan Zhao
collection DOAJ
description 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.
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spelling doaj-art-e75dd5f522754ee5a0390b806ed651852025-08-20T03:01:43ZengNature PortfolioNature Communications2041-17232024-10-0115111710.1038/s41467-024-53609-3Lignin valorization to bioplastics with an aromatic hub metabolite-based autoregulation systemYiquan Zhao0Le Xue1Zhiyi Huang2Zixian Lei3Shiyu Xie4Zhenzhen Cai5Xinran Rao6Ze Zheng7Ning Xiao8Xiaoyu Zhang9Fuying Ma10Hongbo Yu11Shangxian Xie12Department of Biotechnology, College of Life Science and Technology, Huazhong University of Science and TechnologyDepartment of Biotechnology, College of Life Science and Technology, Huazhong University of Science and TechnologyDepartment of Biotechnology, College of Life Science and Technology, Huazhong University of Science and TechnologyDepartment of Biotechnology, College of Life Science and Technology, Huazhong University of Science and TechnologyDepartment of Biotechnology, College of Life Science and Technology, Huazhong University of Science and TechnologyDepartment of Biotechnology, College of Life Science and Technology, Huazhong University of Science and TechnologyDepartment of Biotechnology, College of Life Science and Technology, Huazhong University of Science and TechnologyDepartment of Biotechnology, College of Life Science and Technology, Huazhong University of Science and TechnologyNational key Laboratory of Non-food Biomass Energy Technology, Guangxi Academy of SciencesDepartment of Biotechnology, College of Life Science and Technology, Huazhong University of Science and TechnologyDepartment of Biotechnology, College of Life Science and Technology, Huazhong University of Science and TechnologyDepartment of Biotechnology, College of Life Science and Technology, Huazhong University of Science and TechnologyDepartment of Biotechnology, College of Life Science and Technology, Huazhong University of Science and TechnologyAbstract 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.https://doi.org/10.1038/s41467-024-53609-3
spellingShingle Yiquan Zhao
Le Xue
Zhiyi Huang
Zixian Lei
Shiyu Xie
Zhenzhen Cai
Xinran Rao
Ze Zheng
Ning Xiao
Xiaoyu Zhang
Fuying Ma
Hongbo Yu
Shangxian Xie
Lignin valorization to bioplastics with an aromatic hub metabolite-based autoregulation system
Nature Communications
title Lignin valorization to bioplastics with an aromatic hub metabolite-based autoregulation system
title_full Lignin valorization to bioplastics with an aromatic hub metabolite-based autoregulation system
title_fullStr Lignin valorization to bioplastics with an aromatic hub metabolite-based autoregulation system
title_full_unstemmed Lignin valorization to bioplastics with an aromatic hub metabolite-based autoregulation system
title_short Lignin valorization to bioplastics with an aromatic hub metabolite-based autoregulation system
title_sort lignin valorization to bioplastics with an aromatic hub metabolite based autoregulation system
url https://doi.org/10.1038/s41467-024-53609-3
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