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Background  3-hydroxypropionic acid (3-HP) is an important platform chemical with a wide range of applications. In our previous study, the biosynthetic pathway of 3-HP was constructed and optimized in cyanobacterium  Synechocystis  sp. PCC 6803, which led to 3-HP production directly from CO 2  at a level of 837.18 mg L −1  (348.8 mg/g dry cell weight). As the production and accumulation of 3-HP in cells affect cellular metabolism, a better understanding of cellular responses to 3-HP synthesized internally in  Synechocystis  will be important for further increasing 3-HP productivity in cyanobacterial chassis.    Results  Using a engineered 3-HP-producing SM strain, in this study, the cellular responses to 3-HP internally produced were first determined using a quantitative iTRAQ-LC–MS/MS proteomics approach and a LC–MS-based targeted metabolomics. A total of 2264 unique proteins were identified, which represented about 63 % of all predicted protein in  Synechocystis  in the proteomic analysis; meanwhile intracellular abundance of 24 key metabolites was determined by a comparative metabolomic analysis of the 3-HP-producing strain SM and wild type. Among all identified proteins, 204 proteins were found up-regulated and 123 proteins were found down-regulated, respectively. The proteins related to oxidative phosphorylation, photosynthesis, ribosome, central carbon metabolism, two-component systems and ABC-type transporters were up-regulated, along with the abundance of 14 metabolites related to central metabolism. The results suggested that the supply of ATP and NADPH was increased significantly, and the precursor malonyl-CoA and acetyl-CoA may also be supplemented when 3-HP was produced at a high level in  Synechocystis . Confirmation of proteomic and metabolomic results with RT-qPCR and gene-overexpression strains of selected genes was also conducted, and the overexpression of three transporter genes putatively involved in cobalt/nickel, manganese and phosphate transporting (i.e.,  sll0385 ,  sll1598  and  sll0679 ) could lead to an increased 3-HP production in  Synechocystis .    Conclusions  The integrative analysis of up-regulated proteome and metabolome data showed that to ensure the high-efficient production of 3-HP and the normal growth of  Synechocystis , multiple aspects of cells metabolism including energy, reducing power supply, central carbon metabolism, the stress responses and protein synthesis were enhanced in  Synechocystis . The study provides an important basis for further engineering cyanobacteria for high 3-HP production.    Electronic supplementary material  The online version of this article (doi:10.1186/s13068-016-0627-6) contains supplementary material, which is available to authorized users.

biotechnology for biofuels

Proteomic and metabolomic analyses reveal metabolic responses to 3-hydroxypropionic acid synthesized internally in cyanobacterium Synechocystis sp. PCC 6803