Vibrio natriegens genome-scale modeling reveals insights into halophilic adaptations and resource allocation.

Vibrio natriegens genome-scale modeling reveals insights into halophilic adaptations and resource allocation.
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Vibrio Natriegens基因组规模建模揭示了对卤素适应和资源分配的见解。

DOI:
10.15252/msb.202110523
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发表时间:
2023-04-12
影响因子:
9.9
通讯作者:
--
中科院分区:
生物学1区
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产钠弧菌是一种革兰氏阴性细菌,具有异常的生长速度,有可能成为实验室和工业生物生产的标准生物技术宿主。尽管这种新兴的兴趣,目前缺乏生物体特异性的定性和定量计算工具,阻碍了社区的能力,合理地工程这种细菌。在这项研究中,我们提出了第一个产钠弧菌的基因组规模代谢模型(GSMM)。GSMM(iLC 858)是使用自动化的草案大会和广泛的手工策展开发的,并通过比较预测的产量,中心代谢通量,可行的碳底物,和必需基因与经验数据进行验证。基于质谱的蛋白质组学数据证实,在基本培养基中有氧生长期间,至少76%的预测由模型表达的酶编码基因的翻译。随后使用iLC 858在模式生物大肠杆菌和产钠弧菌之间进行代谢比较,从而分析了产钠弧菌呼吸和ATP生成系统的模型结构,并发现了钠依赖性草酰乙酸脱羧酶泵的作用。蛋白质组学数据进一步用于研究产钠弧菌的其他嗜盐适应。最后,利用iLC 858建立了一个资源平衡分析模型,研究了碳资源的分配。总之,所提出的模型提供了有用的计算工具,以指导产钠弧菌的代谢工程工作。iLC 858是第一个构建和验证的快速生长细菌产钠弧菌的基因组规模代谢模型。这一新模型使产钠弧菌代谢、嗜盐适应和资源分析的研究成为可能。
Vibrio natriegens is a Gram‐negative bacterium with an exceptional growth rate that has the potential to become a standard biotechnological host for laboratory and industrial bioproduction. Despite this burgeoning interest, the current lack of organism‐specific qualitative and quantitative computational tools has hampered the community's ability to rationally engineer this bacterium. In this study, we present the first genome‐scale metabolic model (GSMM) of V. natriegens. The GSMM (iLC858) was developed using an automated draft assembly and extensive manual curation and was validated by comparing predicted yields, central metabolic fluxes, viable carbon substrates, and essential genes with empirical data. Mass spectrometry‐based proteomics data confirmed the translation of at least 76% of the enzyme‐encoding genes predicted to be expressed by the model during aerobic growth in a minimal medium. iLC858 was subsequently used to carry out a metabolic comparison between the model organism Escherichia coli and V. natriegens, leading to an analysis of the model architecture of V. natriegens' respiratory and ATP‐generating system and the discovery of a role for a sodium‐dependent oxaloacetate decarboxylase pump. The proteomics data were further used to investigate additional halophilic adaptations of V. natriegens. Finally, iLC858 was utilized to create a Resource Balance Analysis model to study the allocation of carbon resources. Taken together, the models presented provide useful computational tools to guide metabolic engineering efforts in V. natriegens. iLC858 is the first constructed and validated genome‐scale metabolic model for the fast‐growing bacterium Vibrio natriegens. This new model enabled the study of V. natriegens metabolism, halophilic adaptions, and resource analysis.
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