Genomic mining of plant-induced secondary metabolites in symbiotic cyanobacteria
Final Report Abstract
There is some evidence that the facultative symbolic interaction between nitrogen-fixing Nostoc strains and the symbiotic hosts Blasia pusilla and Gunnera manicata is influenced by chemical negotiations. In the present project, we have systematically analyzed the expression of nonribosomal peptide synthetase (NRPS), polyketide synthase (PKS) and ribosomally produced and posttranslationally modified peptides (RIPPs) during the infection process with both partners. We have constructed a transcriptional reporter library for 16 biosynthetic gene clusters (BGCs) in the model strain N. punctiforme PCC 73102. We could observe a specific response of the secondary metabolite BGCs to chemical or physical interactions with the partners that differed between B. pusilla and G. manicata. In particular, we demonstrated a specific response of different lanthipeptide-BGCs. To upregulate lanthipeptide BGCs, we overexpressed associated transcription factors. Although this approach was not successful for the lanthipeptides themselves we could indirectly upregulate the lanthipeptide BGCs by activating a cell-density-dependent regulatory circuit in N. punctiforme PCC 73102. This work led to the discovery of two groups of new chemical mediators, nostoclides N1 and N2 and nostovalerolactones.
Publications
- (2017) High density cultivation of terrestrial Nostoc strains leads to reprogramming of secondary metabolome. Appl. Environ. Microbiol, 83: e01510-17
Guljamow, A., Kreische, M., Ishida, K., Liaimer, A., Altermark, B., Bähr, L., Hertweck, C., Ehwald, R., Dittmann, E.
(See online at https://doi.org/10.1128/aem.01510-17) - (2019) Unlocking the spatial control of secondary metabolism uncovers hidden natural product diversity in Nostoc punctiforme. ACS Chem Biol. 14: 1271-1279
Dehm, D., Krumbholz, J., Baunach, M., Wiebach, V., Hinrichs, K., Guljamow, A., Tabuchi, R., Jenke-Kodama, H., Süssmuth, R.D., Dittmann, E.
(See online at https://doi.org/10.1021/acschembio.9b00240)