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Investigating Moorella thermoacetica metabolism with a genome-scale constraint-based metabolic model
journal contribution
posted on 2017-11-07, 11:07 authored by Ahsan IslamAhsan Islam, Karsten Zengler, Elizabeth A. Edwards, Radhakrishnan Mahadevan, Gregory StephanopoulosMoorella thermoacetica is a strictly anaerobic, endospore-forming, and metabolically versatile acetogenic
bacterium capable of conserving energy by both autotrophic (acetogenesis) and heterotrophic
(homoacetogenesis) modes of metabolism. Its metabolic diversity and the ability to efficiently convert a wide
range of compounds, including syngas (CO + H2) into acetyl-CoA have made this thermophilic bacterium a
promising host for industrial biotechnology applications. However, lack of detailed information on
M. thermoacetica’s metabolism is a major impediment to its use as a microbial cell factory. In order to
overcome this issue, a genome-scale constraint-based metabolic model of Moorella thermoacetica, iAI558,
has been developed using its genome sequence and physiological data from published literature. The
reconstructed metabolic network of M. thermoacetica comprises 558 metabolic genes, 705 biochemical
reactions, and 698 metabolites. Of the total 705 model reactions, 680 are gene-associated while the rest are
non-gene associated reactions. The model, in addition to simulating both autotrophic and heterotrophic
growth of M. thermoacetica, revealed degeneracy in its TCA-cycle, a common characteristic of anaerobic
metabolism. Furthermore, the model helped elucidate the poorly understood energy conservation
mechanism of M. thermoacetica during autotrophy. Thus, in addition to generating experimentally testable
hypotheses regarding its physiology, such a detailed model will facilitate rapid strain designing and metabolic
engineering of M. thermoacetica for industrial applications.
Funding
Support by the MIT Energy initiative and the DOE Grant (#DE-FOA-0001060) is gratefully acknowledged.
History
School
- Aeronautical, Automotive, Chemical and Materials Engineering
Department
- Chemical Engineering