Nonhierarchical flux regulation exposes the fitness burden associated with lactate production in Synechocystis sp. PCC6803

W. Du, A. Angermayr, J. Jongbloets, D. Molenaar, H. Bachmann, K. Hellingwerf, F. Branco Dos Santos, ACS Synthetic Biology 6 (2017) 395–401.

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Journal Article | Published | English
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Abstract
Cyanobacteria are mostly engineered to be sustainable cell-factories by genetic manipulations alone. Here, by modulating the concentration of allosteric effectors, we focus on increasing product formation without further burdening the cells with increased expression of enzymes. Resorting to a novel 96-well microplate cultivation system for cyanobacteria, and using lactate-producing strains of Synechocystis PCC6803 expressing different l-lactate dehydrogenases (LDH), we titrated the effect of 2,5-anhydro-mannitol supplementation. The latter acts in cells as a nonmetabolizable analogue of fructose 1,6-bisphosphate, a known allosteric regulator of one of the tested LDHs. In this strain (SAA023), we achieved over 2-fold increase of lactate productivity. Furthermore, we observed that as carbon is increasingly deviated during growth toward product formation, there is an increased fixation rate in the population of spontaneous mutants harboring an impaired production pathway. This is a challenge in the development of green cell factories, which may be countered by the incorporation in biotechnological processes of strategies such as the one pioneered here.
Publishing Year
Date Published
2017-03-17
Journal Title
ACS Synthetic Biology
Volume
6
Issue
3
Page
395 - 401
ISSN
IST-REx-ID

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Du W, Angermayr A, Jongbloets J, et al. Nonhierarchical flux regulation exposes the fitness burden associated with lactate production in Synechocystis sp. PCC6803. ACS Synthetic Biology. 2017;6(3):395-401. doi:10.1021/acssynbio.6b00235
Du, W., Angermayr, A., Jongbloets, J., Molenaar, D., Bachmann, H., Hellingwerf, K., & Branco Dos Santos, F. (2017). Nonhierarchical flux regulation exposes the fitness burden associated with lactate production in Synechocystis sp. PCC6803. ACS Synthetic Biology, 6(3), 395–401. https://doi.org/10.1021/acssynbio.6b00235
Du, Wei, Andreas Angermayr, Joeri Jongbloets, Douwe Molenaar, Herwig Bachmann, Klaas Hellingwerf, and Filipe Branco Dos Santos. “Nonhierarchical Flux Regulation Exposes the Fitness Burden Associated with Lactate Production in Synechocystis Sp. PCC6803.” ACS Synthetic Biology 6, no. 3 (2017): 395–401. https://doi.org/10.1021/acssynbio.6b00235.
W. Du et al., “Nonhierarchical flux regulation exposes the fitness burden associated with lactate production in Synechocystis sp. PCC6803,” ACS Synthetic Biology, vol. 6, no. 3, pp. 395–401, 2017.
Du W, Angermayr A, Jongbloets J, Molenaar D, Bachmann H, Hellingwerf K, Branco Dos Santos F. 2017. Nonhierarchical flux regulation exposes the fitness burden associated with lactate production in Synechocystis sp. PCC6803. ACS Synthetic Biology. 6(3), 395–401.
Du, Wei, et al. “Nonhierarchical Flux Regulation Exposes the Fitness Burden Associated with Lactate Production in Synechocystis Sp. PCC6803.” ACS Synthetic Biology, vol. 6, no. 3, American Chemical Society, 2017, pp. 395–401, doi:10.1021/acssynbio.6b00235.

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