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重建泛基因组以预测物种特异性代谢特征。

Pangenome reconstruction of metabolism predicts species-specific metabolic traits.

机构信息

Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Lyngby, Denmark.

Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia.

出版信息

mSystems. 2024 Jul 23;9(7):e0015624. doi: 10.1128/msystems.00156-24. Epub 2024 Jun 26.

Abstract

Strains across the family form the basis for a trillion-dollar industry. Our understanding of the genomic basis for their key traits is fragmented, however, including the metabolism that is foundational to their industrial uses. Pangenome analysis of publicly available genomes allowed us to generate genome-scale metabolic network reconstructions for 26 species of industrial importance. Their manual curation led to more than 75,000 gene-protein-reaction associations that were deployed to generate 2,446 genome-scale metabolic models. Cross-referencing genomes and known metabolic traits allowed for manual metabolic network curation and validation of the metabolic models. As a result, we provide the first pangenomic basis for metabolism in the family and a collection of predictive computational metabolic models that enable a variety of practical uses.IMPORTANCE, a bacterial family foundational to a trillion-dollar industry, is increasingly relevant to biosustainability initiatives. Our study, leveraging approximately 2,400 genome sequences, provides a pangenomic analysis of metabolism, creating over 2,400 curated and validated genome-scale models (GEMs). These GEMs successfully predict (i) unique, species-specific metabolic reactions; (ii) niche-enriched reactions that increase organism fitness; (iii) essential media components, offering insights into the global amino acid essentiality of ; and (iv) fermentation capabilities across the family, shedding light on the metabolic basis of -based commercial products. This quantitative understanding of metabolic properties and their genomic basis will have profound implications for the food industry and biosustainability, offering new insights and tools for strain selection and manipulation.

摘要

家族的菌株是价值万亿美元产业的基础。然而,我们对它们关键特征的基因组基础的理解是零散的,包括对其工业用途至关重要的代谢。通过对公开可用基因组进行泛基因组分析,我们能够为 26 种具有工业重要性的物种生成基因组规模的代谢网络重建。对这些基因组的人工整理导致了超过 75000 个基因-蛋白质-反应关联,这些关联被用来生成 2446 个基因组规模的代谢模型。基因组和已知代谢特征的交叉引用允许对代谢网络进行人工整理和代谢模型的验证。因此,我们提供了家族代谢的第一个泛基因组基础和一系列可用于各种实际用途的预测计算代谢模型。

重要的是,一个对价值万亿美元的产业具有基础性作用的细菌家族,与生物可持续性倡议的关系越来越密切。我们的研究利用了大约 2400 个基因组序列,对代谢进行了泛基因组分析,创建了超过 2400 个经过整理和验证的基因组规模模型 (GEM)。这些 GEM 成功预测了 (i) 独特的、特定于物种的代谢反应;(ii) 增加生物体适应性的生态位丰富反应;(iii) 必需的培养基成分,为提供了对全球必需氨基酸的见解;以及 (iv) 整个家族的发酵能力,揭示了基于代谢的商业产品的代谢基础。对代谢特性及其基因组基础的这种定量理解将对食品工业和生物可持续性产生深远的影响,为菌株选择和操作提供新的见解和工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4740/11265412/36e91db79ec5/msystems.00156-24.f001.jpg

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