@article{WeizIshidaMakoweretal.2011, author = {Weiz, Annika R. and Ishida, Keishi and Makower, Katharina and Ziemert, Nadine and Hertweck, Christian and Dittmann-Th{\"u}nemann, Elke}, title = {Leader Peptide and a Membrane Protein Scaffold Guide the Biosynthesis of the Tricyclic Peptide Microviridin}, series = {Chemistry \& biology}, volume = {18}, journal = {Chemistry \& biology}, number = {11}, publisher = {Cell Press}, address = {Cambridge}, issn = {1074-5521}, doi = {10.1016/j.chembiol.2011.09.011}, pages = {1413 -- 1421}, year = {2011}, abstract = {Microviridins are unique protease inhibitors from bloom-forming cyanobacteria that have both ecological and pharmacological relevance. Their peptide backbones are produced ribosomally, and ATP grasp ligases introduce omega-ester and omega-amide bonds to yield rare cage-like structures. Bioinformatic analysis of the microviridin biosynthesis gene cluster suggests a novel type of processing machinery, which could rationalize the challenging in vivo/in vitro reconstitution of the pathway. In this work, we report the establishment of a minimal expression system for microviridins. Through bioinformatics and mutational analysis of the MdnA leader peptide we identified and characterized a strictly conserved binding motif that is specific for microviridin ligases. Furthermore, we showed that the ABC transporter MdnE is crucial for cyclization and processing of microviridins and demonstrated that MdnE is essential for stability of the microviridin biosynthesis complex.}, 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} }