Experimentally validated reconstruction and analysis of a genome-scale metabolic model of an anaerobic Neocallimastigomycota fungus

Wilken, St. E., Monk, J.M., Leggieri, P.A., Lawson, C.E., Lankiewicz, T.S., Seppälä, S., Daum, C.G., Jenkins, J., Lipzen, A.M., Mondo, S.J., Barry, K.W., Grigoriev, I.V., Henske, J.K., Theodorou, M.K., Palsson, B.O., Petzold, L.R., O’Malley, M.A. and Lindemann, S.R. (2021) Experimentally validated reconstruction and analysis of a genome-scale metabolic model of an anaerobic Neocallimastigomycota fungus. mSystems, 6 (1).

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Anaerobic gut fungi in the phylum Neocallimastigomycota typically inhabit the digestive tracts of large mammalian herbivores, where they play an integral role in the decomposition of raw lignocellulose into its constitutive sugar monomers. However, quantitative tools to study their physiology are lacking, partially due to their complex and unresolved metabolism that includes the largely uncharacterized fungal hydrogenosome. Modern omics approaches combined with metabolic modeling can be used to establish an understanding of gut fungal metabolism and develop targeted engineering strategies to harness their degradation capabilities for lignocellulosic bioprocessing. Here, we introduce a high-quality genome of the anaerobic fungus Neocallimastix lanati from which we constructed the first genome-scale metabolic model of an anaerobic fungus. Relative to its size (200 Mbp, sequenced at 62× depth), it is the least fragmented publicly available gut fungal genome to date. Of the 1,788 lignocellulolytic enzymes annotated in the genome, 585 are associated with the fungal cellulosome, underscoring the powerful lignocellulolytic potential of N. lanati. The genome-scale metabolic model captures the primary metabolism of N. lanati and accurately predicts experimentally validated substrate utilization requirements. Additionally, metabolic flux predictions are verified by 13C metabolic flux analysis, demonstrating that the model faithfully describes the underlying fungal metabolism. Furthermore, the model clarifies key aspects of the hydrogenosomal metabolism and can be used as a platform to quantitatively study these biotechnologically important yet poorly understood early-branching fungi.

Item Type: Article
Keywords: genome-scale metabolic model, 13C metabolic flux analysis, nonmodel fungus, Neocallimastigomycota, flux balance analysis, Neocallimastix lanati, anaerobes, anaerobic fungi
Divisions: Agriculture and Environment (from 1.08.20)
Depositing User: Mrs Rachael Harper
Date Deposited: 08 Apr 2021 09:18
Last Modified: 22 Jul 2021 11:30
URI: https://hau.repository.guildhe.ac.uk/id/eprint/17670

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