Weldon Michael, Euler Christian
Department of Chemical Engineering, University of Waterloo, Waterloo, Canada.
Microb Cell Fact. 2025 Jan 22;24(1):30. doi: 10.1186/s12934-025-02643-x.
Biomanufacturing offers a potentially sustainable alternative to deriving chemicals from fossil fuels. However, traditional biomanufacturing, which uses sugars as feedstocks, competes with food production and yields unfavourable land use changes, so more sustainable options are necessary. Cupriavidus necator is a chemolithoautotrophic bacterium capable of consuming carbon dioxide and hydrogen as sole carbon and energy sources, or formate as the source of both. This autotrophic metabolism potentially makes chemical production using C. necator sustainable and attractive for biomanufacturing. Additionally, C. necator natively fixes carbon in the form of poly-3-hydroxybutyrate, which can be processed to make biodegradable plastic. Recent progress in development of modelling and synthetic biology tools have made C. necator much more usable as a biomanufacturing chassis. However, these tools and applications are often limited by a lack of consideration for the unique physiology and metabolic features of C. necator. As such, further work is required to better understand the intricate mechanisms that allow it to prioritise generalization over specialization. In this review, progress toward physiology-informed engineering of C. necator across several dimensions is critically discussed, and recommendations for moving toward a physiological approach are presented. Arguments for metabolic specialization, more focus on autotrophic fermentation, C. necator-specific synthetic biology tools, and modelling that goes beyond constraints are presented based on analysis of existing literature.
生物制造为从化石燃料中提取化学物质提供了一种潜在的可持续替代方案。然而，传统的生物制造以糖为原料，与粮食生产竞争，并导致不利的土地利用变化，因此需要更可持续的选择。食酸丛毛单胞菌是一种化能自养细菌，能够以二氧化碳和氢气作为唯一的碳源和能源，或以甲酸盐作为两者的来源。这种自养代谢可能使利用食酸丛毛单胞菌进行化学生产具有可持续性，并对生物制造具有吸引力。此外，食酸丛毛单胞菌天然地以聚-3-羟基丁酸酯的形式固定碳，聚-3-羟基丁酸酯可被加工制成可生物降解塑料。建模和合成生物学工具开发方面的最新进展使食酸丛毛单胞菌作为生物制造底盘更具实用性。然而，这些工具和应用往往受到对食酸丛毛单胞菌独特的生理学和代谢特征缺乏考虑的限制。因此，需要进一步开展工作，以更好地理解使其能够优先进行泛化而非特化的复杂机制。在这篇综述中，我们批判性地讨论了在几个维度上对食酸丛毛单胞菌进行生理学信息工程的进展，并提出了转向生理学方法的建议。基于对现有文献的分析，提出了代谢特化、更多关注自养发酵、食酸丛毛单胞菌特异性合成生物学工具以及超越限制的建模等观点。
