Data_Sheet_3_High-Quality Genome-Scale Reconstruction of Corynebacterium glutamicum ATCC 13032.CSV

Corynebacterium glutamicum belongs to the microbes of enormous biotechnological relevance. In particular, its strain ATCC 13032 is a widely used producer of L-amino acids at an industrial scale. Its apparent robustness also turns it into a favorable platform host for a wide range of further compounds, mainly because of emerging bio-based economies. A deep understanding of the biochemical processes in C. glutamicum is essential for a sustainable enhancement of the microbe's productivity. Computational systems biology has the potential to provide a valuable basis for driving metabolic engineering and biotechnological advances, such as increased yields of healthy producer strains based on genome-scale metabolic models (GEMs). Advanced reconstruction pipelines are now available that facilitate the reconstruction of GEMs and support their manual curation. This article presents iCGB21FR, an updated and unified GEM of C. glutamicum ATCC 13032 with high quality regarding comprehensiveness and data standards, built with the latest modeling techniques and advanced reconstruction pipelines. It comprises 1042 metabolites, 1539 reactions, and 805 genes with detailed annotations and database cross-references. The model validation took place using different media and resulted in realistic growth rate predictions under aerobic and anaerobic conditions. The new GEM produces all canonical amino acids, and its phenotypic predictions are consistent with laboratory data. The in silico model proved fruitful in adding knowledge to the metabolism of C. glutamicum: iCGB21FR still produces L-glutamate with the knock-out of the enzyme pyruvate carboxylase, despite the common belief to be relevant for the amino acid's production. We conclude that integrating high standards into the reconstruction of GEMs facilitates replicating validated knowledge, closing knowledge gaps, and making it a useful basis for metabolic engineering. The model is freely available from BioModels Database under identifier MODEL2102050001.

谷氨酸棒杆菌（Corynebacterium glutamicum）是一类具有极高生物技术价值的微生物。其中，ATCC 13032菌株是工业化规模化生产L-氨基酸的经典通用宿主。凭借优异的抗逆性能，该菌株也因新兴生物基经济的发展，成为合成各类下游化合物的理想平台宿主。深入解析谷氨酸棒杆菌体内的生化代谢过程，对可持续提升其生产性能至关重要。计算系统生物学可为代谢工程与生物技术革新提供重要支撑：例如基于基因组尺度代谢模型（genome-scale metabolic models, GEMs）构建高产且健康的工程菌株，以提升目标产物的合成得率。当前已有成熟的先进重构流程，可辅助完成GEMs的构建，并支持后续的手动注释与优化工作。本文报道了iCGB21FR：一款针对谷氨酸棒杆菌ATCC 13032的更新版统一化基因组尺度代谢模型，其构建采用最新建模技术与先进重构流程，在模型全面性与数据规范性上均达到行业较高水准。该模型共包含1042种代谢物、1539个反应以及805个编码基因，且带有详细的功能注释与多数据库交叉引用信息。模型验证环节采用多种培养基体系开展，结果显示其在有氧与厌氧条件下均可生成符合实际的生长速率预测值。该新版GEM可合成所有经典氨基酸，表型预测结果与实验室实测数据高度吻合。此外，该虚拟模型还为解析谷氨酸棒杆菌的代谢机制带来了新的认知突破：此前学界普遍认为丙酮酸羧化酶对L-谷氨酸的合成至关重要，但敲除该酶后，iCGB21FR仍可正常生成L-谷氨酸。综上，在基因组尺度代谢模型的重构过程中引入高标准的规范流程，可有效复现已验证的生物学认知、填补现有知识空白，并为代谢工程研究提供可靠的研究基础。该模型可通过标识符MODEL2102050001在生物模型数据库（BioModels Database）中免费获取。