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Engineering microbial cell factories for succinic acid biomanufacturing: Challenges and perspectives
Ling-Ling Bai1, Na Li1, Jing-Ru Yang1
1State Key Laboratory of Synthetic Biology, Tianjin University, Tianjin, China; Frontiers Science Center for Synthetic Biology (Ministry of Education), Tianjin University, Tianjin, China; School of Synthetic Biology and Biomanufacturing, Tianjin University, Tianjin, China.
None:
Succinic acid, a key platform chemical derived from renewable substrates, represents a sustainable alternative to petrochemical production. Microbial biosynthesis has emerged as a promising route for bio-based succinic acid production, offering a paradigm shift through its utilization of renewable substrates. This review systematically evaluates microbial platforms, including some bacteria and yeasts, comparing their physiological traits, metabolic capabilities, and suitability for industrial succinic acid production. Subsequent sections discuss the rational design of native and heterologous biosynthesis pathways aligned with host-specific characteristics, advanced synthetic biology tools for enhancing chassis performance and pathway compatibility, and innovations in downstream separation to improve process economics. Finally, the review emphasizes the integrative application of systems biology, metabolic modeling, and process engineering to address persistent challenges in carbon flux optimization, redox balancing, and industrial scaling. By offering a multidisciplinary perspective on strain development and bioprocess integration, this review provides a strategic framework for advancing the design of efficient microbial cell factories and accelerating the commercialization of bio-based succinic acid.
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