微生物固碳能量-碳流耦合定量评价及多尺度协同设计

Quantitative evaluation of energy-carbon flux coupling and multi-scale synergistic design for microbial carbon fixation

摘要:

将CO₂高效转化为燃料与化学品是实现可持续生物制造的重要路径，微生物细胞工厂在其中具有广阔应用前景。然而，尽管固碳途径设计与碳流重构不断进展，体系性能仍主要受限于能量供给与利用效率，其根本在于能量代谢与碳固定之间在能量载体形式[ATP、NAD(P)H及低电势电子]、供给比例及氧化还原电势上的系统性失配，从而限制碳通量与能量利用效率。本文从能量-碳流耦合视角出发，提出能量转化链条框架，将固碳过程统一为能量输入、电子传递与碳同化过程的级联网络，并建立涵盖能量输入效率(energy input efficiency, EE)、电子利用效率(redox/electron utilization efficiency, RE)及能量-碳转化效率(energy-to-carbon conversion efficiency, ECE)的定量评价体系。结合实验测量与代谢建模，系统解析能量载体分布与电子流动特征，识别出关键瓶颈，包括能量输入通量、电子传递损耗、辅因子失配及反应网络效率等。在工程层面，进一步总结底盘宿主选择、外源供能模块构建及内源能量网络重构等策略，并提出多尺度能量-碳流协同设计框架，实现能量供给与固碳需求的精准匹配。总体而言，本综述从系统层面重塑能量在固碳工程中的核心地位，为构建高效、稳定的CO₂生物转化体系提供了理论基础与工程路径。

Abstract:

The efficient conversion of CO₂ into fuels and chemicals represents a key route toward sustainable biomanufacturing, and microbial cell factories offer significant potential for this purpose. Despite substantial advances in carbon fixation pathway design and carbon flux rewiring, the performance of microbial CO₂-fixing systems remains largely constrained by the efficiency of energy supply and utilization. At the core of this limitation is a systemic mismatch between energy metabolism and carbon fixation, involving discrepancies in energy carrier types [ATP, NAD(P)H, and low-potential electrons], supply ratios, and redox potential, which ultimately restrict carbon flux and energy utilization efficiency. From the perspective of energy-carbon flux coupling, this review proposes an energy conversion chain framework that conceptualizes carbon fixation as a cascade network comprising energy input, electron transfer, and carbon assimilation. On the basis of this framework, a quantitative evaluation system is established, encompassing energy input efficiency (EE), redox/electron utilization efficiency (RE), and energy-to-carbon conversion efficiency (ECE). By integrating experimental measurements with metabolic modeling, we systematically analyze the distribution of energy carriers and electron fluxes and identify key bottlenecks, including limitations in energy input flux, electron transfer losses, cofactor mismatches, and reaction network efficiency. At the engineering level, we further summarize strategies for improving energy-carbon compatibility, including chassis selection under energy constraints, construction of exogenous energy-supplying modules, and rewiring of endogenous energy networks. Building upon these advances, a multi-scale energy-carbon co-design framework is proposed to achieve precise matching between energy supply and carbon fixation demand. Overall, this review redefines energy metabolism as a central design dimension in carbon fixation engineering and provides both a theoretical foundation and engineering strategies for the development of efficient and robust CO₂ bioconversion systems.