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Zymomonas mobilis Metabolic Engineering For Improved Production And Stress Tolerance

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Zymomonas mobilis is a facultatively anaerobic alpha-proteobacterium, possessing the most rapid ethanologenic pathway among the known microorganisms. The highly efficient Entner-Doudoroff pathway, together with pyruvate decarboxylase and alcohol dehydrogenase, form the backbone of Z. mobilis catabolism. ...

Zymomonas mobilis is a facultatively anaerobic alpha-proteobacterium, possessing the most rapid ethanologenic pathway among the known microorganisms. The highly efficient Entner-Doudoroff pathway, together with pyruvate decarboxylase and alcohol dehydrogenase, form the backbone of Z. mobilis catabolism. Central metabolism of Z. mobilis, with its truncated Krebs cycle and incomplete pentose phosphate pathway, is simpler than that of E. coli, not to mention yeast. Catabolism in this bacterium is largely uncoupled from the anabolic demand, and hence, up to 98% of substrate carbon gets incorporated in ethanol. Also, its respiratory metabolism is poorly coupled: compared to E. coli and Saccharomyces cerevisiae respiration, Z. mobilis has a higher rate of oxygen consumption, yet lower yield of ATP.

Apart from the high rate and yield of ethanol synthesis, advantages of Z. mobilis for industrial application include its high ethanol tolerance, ability to produce ethanol across a broad pH range, growth in media with high sugar concentrations, ability to fix atmospheric nitrogen, as well as the fact that this bacterium is generally regarded as safe (GRAS).

During the last three decades, these traits of Z. mobilis have promoted metabolic engineering work on bioethanol production from renewable substrates, as well as efforts to increase its robustness to medium constituents and environmental conditions, like inhibitory compounds and elevated temperature. However, a lot still needs to be done in order to exploit the full biotechnological potential of this bacterium. For the industrial, lignocellulose-based ethanol production process to be economically feasible, pentose sugar fermentations by Z. mobilis recombinant strains must be improved, in line with raising of strain resistance to the variety of toxic compounds present in the lignocellulosic hydrolysates. Secondly, it seems tempting to redirect the Z. mobilis powerful ‘catabolic highway’ towards the production of various value-added biochemicals other than ethanol. Unfortunately, so far the yields and titers of alternative products are much lower compared to that of ethanol.
Clearly, more insight is needed into the control and regulation of Z. mobilis catabolism to overcome these limitations. Engineering of the respiratory chain of this bacterium also can contribute both to the broadening of the product spectrum and to the oxidative and temperature stress resistance.

With the availability of a number of Z. mobilis genomes, systems biology approach has gained momentum and provided rational guidelines for strain improvement. Several medium- and genome-scale metabolic models for Z. mobilis have been constructed and serve for rational metabolic engineering of this bacterium, in combination with comparative genomics, transcriptomics, proteomics, metabolomics, and high-throughput genetics. Complementary to the rational engineering, Z. mobilis has been subject to mutagenesis and directed evolution, and genome-resequencing analysis is applied to identify the underlying genetic changes responsive to the altered phenotypes.

In summary, the present work on broadening Z. mobilis substrate and product spectra, and raising its productivity and robustness increasingly relies upon novel genomic, systems biology and synthetic biology methodologies. The aim of this Research Topic is to reveal the latest trends and achievements in this field.


Keywords: Zymomonas mobilis, Lignocellulosic Biomass, Biofuels, Stress Response, Respiratory Me-tabolism


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