Expression of Formate-Tetrahydrofolate Ligase Did Not Improve Growth but Interferes With Nitrogen and Carbon Metabolism of Synechocystis sp. PCC 6803

The introduction of alternative CO2-fixing pathways in photoautotrophic organism may improve the efficiency of biological carbon fixation such as minimizing the carbon loss due to photorespiration. Here, we analyzed the effects of creating a formate entry point into the primary metabolism of the cyanobacteriumSynechocystissp. PCC 6803. The formate-tetrahydrofolate ligase (FTL) fromMethylobacterium extorquensAM1 was expressed inSynechocystisto enable formate assimilation and reducing the loss of fixed carbon in the photorespiratory pathway. Transgenic strains accumulated serine and 3-phosphoglycerate, and consumed more 2-phosphoglycolate and glycine, which seemed to reflect an efficient utilization of formate. However, labeling experiments showed that the serine accumulation was not due to the expected incorporation of formate. Subsequent DNA-microarray analysis revealed profound changes in transcript abundance due toftlexpression. Transcriptome changes were observed in relation to serine and glycine metabolism, C1-metabolism and particularly nitrogen assimilation. The data implied thatftlexpression interfered with the signaling the carbon/nitrogen ratio inSynechocystis. Our results indicate that the expression of new enzymes could have a severe impact on the cellular regulatory network, which potentially hinders the establishment of newly designed pathways.