title: On the use of metabolic control analysis in the optimization of cyanobacterial biosolar cell factories.
abstract: Oxygenic photosynthesis will have a key role in a sustainable future. It is therefore significant that this process can be engineered in organisms such as cyanobacteria to construct cell factories that catalyze the (sun)light-driven conversion of CO2 and water into products like ethanol, butanol, or other biofuels or lactic acid, a bioplastic precursor, and oxygen as a byproduct. It is of key importance to optimize such cell factories to maximal efficiency. This holds for their light-harvesting capabilities under, for example, circadian illumination in large-scale photobioreactors. However, this also holds for the "dark" reactions of photosynthesis, that is, the conversion of CO2, NADPH, and ATP into a product. Here, we present an analysis, based on metabolic control theory, to estimate the optimal capacity for product formation with which such cyanobacterial cell factories have to be equipped. Engineered l-lactic acid producing Synechocystis sp. PCC6803 strains are used to identify the relation between production rate and enzymatic capacity. The analysis shows that the engineered cell factories for l-lactic acid are fully limited by the metabolic capacity of the product-forming pathway. We attribute this to the fact that currently available promoter systems in cyanobacteria lack the genetic capacity to a provide sufficient expression in single-gene doses.
authors.affiliation: Molecular Microbial Physiology Group, Swammerdam Institute for Life Sciences, University of Amsterdam and Netherlands Institute of Systems Biology , The Netherlands.
authors.forename: S Andreas
authors.initials: SA
authors.lastname: Angermayr
authors.forename: Klaas J
authors.initials: KJ
authors.lastname: Hellingwerf
mesh_terms: D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D056804:Biofuels; D018533:Biomass; D002245:Carbon Dioxide / Q000737:chemistry / Q000378:metabolism; D000458:Cyanobacteria / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D017045:Lactococcus / Q000201:enzymology; D011401:Promoter Regions, Genetic
chemical_list: D001426:Bacterial Proteins; D056804:Biofuels; D002245:Carbon Dioxide; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase