From metagenomes to metabolism: Systematically assessing the metabolic flux feasibilities for "Candidatus Accumulibacter" species during anaerobic substrate uptake.

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Title: From metagenomes to metabolism: Systematically assessing the metabolic flux feasibilities for "Candidatus Accumulibacter" species during anaerobic substrate uptake.
Authors: Páez-Watson, Timothy1 (AUTHOR) T.W.PaezWatson@tudelft.nl, van Loosdrecht, Mark C.M.1 (AUTHOR), Wahl, S.Aljoscha1 (AUTHOR)
Source: Water Research. Feb2024, Vol. 250, pN.PAG-N.PAG. 1p.
Subjects: Metabolic models, Candidatus, Carbon metabolism, Species, Calcium metabolism, Medium density fiberboard
Abstract: • MAG-only inference does not consider thermodynamic infeasibilities. • " Ca. Accumulibacter" species exhibit distinct potential in central carbon metabolism. • Anaerobic classical TCA cycle is thermodynamically infeasible. • PHA accumulation balances thermodynamic feasibility and yield. With the rapid growing availability of metagenome assembled genomes (MAGs) and associated metabolic models, the identification of metabolic potential in individual community members has become possible. However, the field still lacks an unbiassed systematic evaluation of the generated metagenomic information to uncover not only metabolic potential, but also feasibilities of these models under specific environmental conditions. In this study, we present a systematic analysis of the metabolic potential in species of " Candidatus Accumulibacter", a group of polyphosphate-accumulating organisms (PAOs). We constructed a metabolic model of the central carbon metabolism and compared the metabolic potential among available MAGs for " Ca. Accumulibacter" species. By combining Elementary Flux Modes Analysis (EFMA) with max-min driving force (MDF) optimization, we obtained all possible flux distributions of the metabolic network and calculated their individual thermodynamic feasibility. Our findings reveal significant variations in the metabolic potential among " Ca. Accumulibacter" MAGs, particularly in the presence of anaplerotic reactions. EFMA revealed 700 unique flux distributions in the complete metabolic model that enable the anaerobic uptake of acetate and its conversion into polyhydroxyalkanoates (PHAs), a well-known phenotype of " Ca. Accumulibacter". However, thermodynamic constraints narrowed down this solution space to 146 models that were stoichiometrically and thermodynamically feasible (MDF > 0 kJ/mol), of which only 8 were strongly feasible (MDF > 7 kJ/mol). Notably, several novel flux distributions for the metabolic model were identified, suggesting putative, yet unreported, functions within the PAO communities. Overall, this work provides valuable insights into the metabolic variability among " Ca. Accumulibacter" species and redefines the anaerobic metabolic potential in the context of phosphate removal. More generally, the integrated workflow presented in this paper can be applied to any metabolic model obtained from a MAG generated from microbial communities to objectively narrow the expected phenotypes from community members. [Display omitted] [ABSTRACT FROM AUTHOR]
Copyright of Water Research is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: From metagenomes to metabolism: Systematically assessing the metabolic flux feasibilities for "Candidatus Accumulibacter" species during anaerobic substrate uptake.
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  Data: • MAG-only inference does not consider thermodynamic infeasibilities. • " Ca. Accumulibacter" species exhibit distinct potential in central carbon metabolism. • Anaerobic classical TCA cycle is thermodynamically infeasible. • PHA accumulation balances thermodynamic feasibility and yield. With the rapid growing availability of metagenome assembled genomes (MAGs) and associated metabolic models, the identification of metabolic potential in individual community members has become possible. However, the field still lacks an unbiassed systematic evaluation of the generated metagenomic information to uncover not only metabolic potential, but also feasibilities of these models under specific environmental conditions. In this study, we present a systematic analysis of the metabolic potential in species of " Candidatus Accumulibacter", a group of polyphosphate-accumulating organisms (PAOs). We constructed a metabolic model of the central carbon metabolism and compared the metabolic potential among available MAGs for " Ca. Accumulibacter" species. By combining Elementary Flux Modes Analysis (EFMA) with max-min driving force (MDF) optimization, we obtained all possible flux distributions of the metabolic network and calculated their individual thermodynamic feasibility. Our findings reveal significant variations in the metabolic potential among " Ca. Accumulibacter" MAGs, particularly in the presence of anaplerotic reactions. EFMA revealed 700 unique flux distributions in the complete metabolic model that enable the anaerobic uptake of acetate and its conversion into polyhydroxyalkanoates (PHAs), a well-known phenotype of " Ca. Accumulibacter". However, thermodynamic constraints narrowed down this solution space to 146 models that were stoichiometrically and thermodynamically feasible (MDF > 0 kJ/mol), of which only 8 were strongly feasible (MDF > 7 kJ/mol). Notably, several novel flux distributions for the metabolic model were identified, suggesting putative, yet unreported, functions within the PAO communities. Overall, this work provides valuable insights into the metabolic variability among " Ca. Accumulibacter" species and redefines the anaerobic metabolic potential in the context of phosphate removal. More generally, the integrated workflow presented in this paper can be applied to any metabolic model obtained from a MAG generated from microbial communities to objectively narrow the expected phenotypes from community members. [Display omitted] [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Water Research is the property of Pergamon Press - An Imprint of Elsevier Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1016/j.watres.2023.121028
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      – Code: eng
        Text: English
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        Type: general
      – SubjectFull: Candidatus
        Type: general
      – SubjectFull: Carbon metabolism
        Type: general
      – SubjectFull: Species
        Type: general
      – SubjectFull: Calcium metabolism
        Type: general
      – SubjectFull: Medium density fiberboard
        Type: general
    Titles:
      – TitleFull: From metagenomes to metabolism: Systematically assessing the metabolic flux feasibilities for "Candidatus Accumulibacter" species during anaerobic substrate uptake.
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            NameFull: van Loosdrecht, Mark C.M.
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              M: 02
              Text: Feb2024
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