@article{DehmKrumbholzBaunachetal.2019,
  author    = {Dehm, Daniel and Krumbholz, Julia and Baunach, Martin and Wiebach, Vincent and Hinrichs, Katrin and Guljamow, Arthur and Tabuchi, Takeshi and Jenke-Kodama, Holger and S{\"u}ssmuth, Roderich D. and Dittmann-Th{\"u}nemann, Elke},
  title     = {Unlocking the spatial control of secondary metabolism uncovers hidden natural product diversity in nostoc punctiforme},
  series = {ACS chemical biology},
  volume    = {14},
  journal   = {ACS chemical biology},
  number    = {6},
  publisher = {American Chemical Society},
  address   = {Washington},
  issn      = {1554-8929},
  doi       = {10.1021/acschembio.9b00240},
  pages     = {1271 -- 1279},
  year      = {2019},
  abstract  = {Filamentous cyanobacteria belong to the most prolific producers of structurally unique and biologically active natural products, yet the majority of biosynthetic gene clusters predicted for these multicellular collectives are currently orphan. Here, we present a systems analysis of secondary metabolite gene expression in the model strain Nostoc punctiforme PCC73102 using RNA-seq and fluorescence reporter analysis. Our data demonstrate that the majority of the cryptic gene clusters are not silent but are expressed with regular or sporadic pattern. Cultivation of N. punctiforme using high-density fermentation overrules the spatial control and leads to a pronounced upregulation of more than 50\% of biosynthetic gene clusters. Our data suggest that a combination of autocrine factors, a high CO2 level, and high light account for the upregulation of individual pathways. Our overarching study not only sheds light on the strategies of filamentous cyanobacteria to share the enormous metabolic burden connected with the production of specialized molecules but provides an avenue for the genome-based discovery of natural products in multicellular cyanobacteria as exemplified by the discovery of highly unusual variants of the tricyclic peptide microviridin.},
  language  = {en}
}
@article{LiaimerJenkeKodamaIshidaetal.2011,
  author    = {Liaimer, Anton and Jenke-Kodama, Holger and Ishida, Keishi and Hinrichs, Katrin and Stangeland, Janne and Hertweck, Christian and Dittmann-Th{\"u}nemann, Elke},
  title     = {A polyketide interferes with cellular differentiation in the symbiotic cyanobacterium Nostoc punctiforme},
  series = {Environmental microbiology reports},
  volume    = {3},
  journal   = {Environmental microbiology reports},
  number    = {5},
  publisher = {Wiley-Blackwell},
  address   = {Malden},
  issn      = {1758-2229},
  doi       = {10.1111/j.1758-2229.2011.00258.x},
  pages     = {550 -- 558},
  year      = {2011},
  abstract  = {Nostoc punctiforme is a filamentous cyanobacterium capable of forming symbiotic associations with a wide range of plants. The strain exhibits extensive phenotypic characteristics and can differentiate three mutually exclusive cell types: nitrogen-fixing heterocysts, motile hormogonia and spore-like akinetes. Here, we provide evidence for a crucial role of an extracellular metabolite in balancing cellular differentiation. Insertional mutagenesis of a gene of the polyketide synthase gene cluster pks2 led to the accumulation of short filaments carrying mostly terminal heterocysts under diazotrophic conditions. The mutant has a strong tendency to form biofilms on solid surfaces as well as in liquid culture. The pks2-strain keeps forming hormogonia over the entire growth curve and shows an early onset of akinete formation. We could isolate two fractions of the wildtype supernatant that could restore the capability to form long filaments with intercalary heterocysts. Growth of the mutant cells in the neighbourhood of wild-type cells on plates led to a reciprocal influence and a partial reconstruction of wild-type and mutant phenotype respectively. We postulate that extracellular metabolites of Nostoc punctiforme act as life cycle governing factors (LCGFs) and that the ratio between distinct factors may guide the differentiation into different life stages.},
  language  = {en}
}