Title: Uncertainty Quantification of Bacterial Microcompartment Permeability Show Chinese title

Title: 细菌微区室渗透性的不确定性量化

Abstract: $\textit{Salmonella}$ expresses bacterial microcompartments (MCPs) upon 1,2-propanediol exposure. MCPs are nanoscale protein-bound shells that encase enzymes for the cofactor-dependent 1,2-propanediol metabolism. They are hypothesized to limit exposure to the toxic intermediate, propionaldehyde, decrease cofactor involvement in competing reactions, and enhance flux. We construct a mass-action mathematical model of purified MCPs and calibrate parameters to measured metabolite concentrations. We constrain mass-action kinetic parameters to previously estimated Michaelis-Menten parameters. We identified two distinct fits with different dynamics in the pathway product, propionate, but similar goodness of fit. Across fits, we inferred that the MCP 1,2-propanediol and propionaldehyde permeability should be greater than $10^{-6}$ and $10^{-8}$ m/s, respectively. Our results identify parameter ranges consistent with prevailing theories that MCPs impose preferential diffusion to 1,2-propanediol over propionaldehyde, and sequester toxic propionaldehyde away from the cell cytosol. The bimodality of the posterior distribution arises from bimodality in the estimated coenzyme-A (CoA) permeability and inhibition rates. The MCP permeability to CoA was inferred to be either less than $10^{-8.8}$ m/s or greater than $10^{-7.3}$ m/s. In a high CoA permeability environment with low rates of CoA inhibition, enzymes produced metabolites by recycling (NAD+)/(NADH). In a low CoA permeability environment with high rates of CoA inhibition, enzymes required external NAD+/H to produce metabolites. Dynamics are consistent with prevailing hypotheses about MCP function to sequester toxic propionaldehyde, and additional collection of data points between 6 and 24 hours or characterization of enzyme inhibition rates could further reduce uncertainty and provide better permeability estimates. Show Chinese abstract

Abstract: $\textit{Salmonella}$在1,2-丙二醇暴露时表达细菌微区室（MCPs）。 MCPs 是纳米级的蛋白包被壳，包裹酶用于辅因子依赖的1,2-丙二醇代谢。 它们被认为可以限制对有毒中间体丙醛的暴露，减少辅因子在竞争反应中的参与，并增强通量。 我们构建了一个纯化的MCP质量作用数学模型，并将参数校准为测得的代谢物浓度。 我们将质量作用动力学参数限制为先前估计的米氏方程参数。 我们发现了两种不同的拟合，路径产物丙酸有不同的动态，但相似的拟合优度。 在所有拟合中，我们推断出MCP对1,2-丙二醇和丙醛的渗透性应分别大于$10^{-6}$和$10^{-8}$m/s。 我们的结果确定了与现有理论一致的参数范围，即MCP对1,2-丙二醇的扩散优先于丙醛，并将有毒的丙醛从细胞质中隔离出来。 后验分布的双峰性来自于辅酶A（CoA）渗透性和抑制率的估计双峰性。 MCP对CoA的渗透性被推断为小于$10^{-8.8}$m/s 或大于$10^{-7.3}$m/s。 在高CoA渗透性环境且低CoA抑制速率下，酶通过回收（NAD+）/(NADH)产生代谢物。 在低CoA渗透性环境且高CoA抑制速率下，酶需要外部的NAD+/H来产生代谢物。 动态与关于MCP功能以隔离有毒的丙醛的现有假设一致，进一步收集6到24小时之间的数据点或表征酶抑制速率可以进一步减少不确定性并提供更好的渗透性估计。