Reconstruction and Analysis of a Genome-wide Metabolic Model of Sulfurospirillum multivorans

Supplementary information

rec_progress.csv - Manual curation documentation

cyc_access.py - lib for cyc2sbml

cyc2sbml.py - python script to export data from pathwaytools to sbml

sm.xml - sbml model of S. multivorans (bounds are set to a growth with 20mM pyruvate and 5% oxygen)

smul-26_extended.xml - raw sbml model of S. multivorans (has to be complemented and run by test.py)

test.py - python script to read, complement and simulate the sbml model of S. multivorans

The recently sequenced and annotated genome of Sulfurospirillum multivorans provides insight into a versatile metabolism. For instance, S. multivorans can mediate organohalide respiration which is a useful bioremediation process to degrade carcinogens like tetra chloroethene. Furthermore, a wide range of of electron donor oxidizing and electron acceptor reducing enzymes was identi?ed in S. multivorans and even oxygen can be used as terminal electron acceptor which is unusual for organohalide respiring organisms. Herein, I want to present a metabolic reconstruction of S. multivorans based on the genome annotation and experimental as well as expert knowledge. In total, it accounts for 761 metabolic genes, 1266 reactions and 995 metabolites. The reconstruction was used to derive a computational model of the metabolism of S. multivorans: Given a certain growth condition, a method called Flux Balance Analysis was applied to predict reaction flows in mmol g^−1 h−1 (gram dry weight) for each reconstructed reaction. Thus, a set of active reactions can be inferred that enables a specific phenotype. Simulations were compared to experimental findings and suggestions for open research topics (carbon unbalance) were made.

补充信息

rec_progress.csv —— 人工整理文档
cyc_access.py —— 用于cyc2sbml的工具库
cyc2sbml.py —— 用于从PathwayTools导出数据至SBML（Systems Biology Markup Language，系统生物学标记语言）的Python脚本
sm.xml —— 多嗜硫螺菌（Sulfurospirillum multivorans）的SBML模型，其约束条件设置为以20mM丙酮酸盐与5%氧气为底物进行生长的状态
smul-26_extended.xml —— 多嗜硫螺菌的原始SBML模型，需通过test.py完成补全与运行
test.py —— 用于读取、补全并模拟多嗜硫螺菌SBML模型的Python脚本

近期完成测序与注释的多嗜硫螺菌（Sulfurospirillum multivorans）基因组，为解析其多样化的代谢模式提供了重要研究基础。例如，该菌可介导有机卤呼吸这一高效生物修复过程，能够降解四氯乙烯等致癌污染物。此外，研究团队在该菌中鉴定出大量可氧化电子供体、还原电子受体的酶类，且其甚至可将氧气作为末端电子受体——这一特性对于有机卤呼吸型微生物而言极为罕见。
本研究基于该菌的基因组注释信息、实验数据与领域专家知识，构建了多嗜硫螺菌的代谢重构模型。该模型共涵盖761个代谢基因、1266个反应与995种代谢物。
基于该代谢重构模型，研究者进一步搭建了多嗜硫螺菌的代谢计算模型：在特定生长条件下，通过通量平衡分析（Flux Balance Analysis）方法，可针对每个重构反应预测其以mmol·g⁻¹·h⁻¹（克干重）为单位的反应通量。由此可推导出一组可产生特定表型的活跃反应集合。
研究将模拟结果与实验观测数据进行了对比，并针对现存研究空白（如碳失衡问题）提出了后续研究方向。