title: Engineering a cyanobacterial cell factory for production of lactic acid.
abstract: Metabolic engineering of microorganisms has become a versatile tool to facilitate production of bulk chemicals, fuels, etc. Accordingly, CO(2) has been exploited via cyanobacterial metabolism as a sustainable carbon source of biofuel and bioplastic precursors. Here we extended these observations by showing that integration of an ldh gene from Bacillus subtilis (encoding an l-lactate dehydrogenase) into the genome of Synechocystis sp. strain PCC6803 leads to l-lactic acid production, a phenotype which is shown to be stable for prolonged batch culturing. Coexpression of a heterologous soluble transhydrogenase leads to an even higher lactate production rate and yield (lactic acid accumulating up to a several-millimolar concentration in the extracellular medium) than those for the single ldh mutant. The expression of a transhydrogenase alone, however, appears to be harmful to the cells, and a mutant carrying such a gene is rapidly outcompeted by a revertant(s) with a wild-type growth phenotype. Furthermore, our results indicate that the introduction of a lactate dehydrogenase rescues this phenotype by preventing the reversion.
authors.affiliation: Swammerdam Institute for Life Sciences and Netherlands Institute for Systems Biology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: S Andreas
authors.initials: SA
authors.lastname: Angermayr
authors.forename: Michal
authors.initials: M
authors.lastname: Paszota
authors.forename: Klaas J
authors.initials: KJ
authors.lastname: Hellingwerf
mesh_terms: D001412:Bacillus subtilis / Q000201:enzymology / Q000235:genetics; D042822:Genomic Instability; D007770:L-Lactate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism*; D060847:Metabolic Engineering; D050296:Microbial Viability; D009250:NADP Transhydrogenases / Q000235:genetics / Q000378:metabolism; D046939:Synechocystis / Q000235:genetics* / Q000378:metabolism*
chemical_list: D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase; D009250:NADP Transhydrogenases