Identification and functional characterization of cryptic secondary metabolite gene clusters and comparative genomics in Fusarium fujikuroi
Final Report Abstract
The increasing number of sequenced fungal genomes revealed the enormous potential of fungi to produce a multitude of natural products. However, the majority of SM gene clusters are silent under laboratory conditions, and therefore, their products are still unknown. The growing interest in identification of novel fungal SMs with potential applications in medicine, food industry and agriculture resulted in efforts to activate them by using different molecular techniques. During the last years, we tried to shed more light into the genetic potential of the rice pathogenic fungus F. fujikuroi.to produce new SMs. Whereas only three gene clusters for GA, bikaverin and carotenoid biosynthesis were identified and experimentally characterized before the genome has been released in 2013, the products of 20 out of the 47 potential SM gene clusters are now known due to genetic manipulations of key enzyme-encoding genes, pathway-specific and global regulators, and histone-modifying genes. By these approaches we were able to shed more light on the multi-level regulation of secondary metabolism. One of the most surprising results of these studies is that each single gene cluster is regulated by a specific und unique network of regulators. A second topic of this application period was a comparative genomics approach to determine the level of variability between F. fujikuroi isolates from distinct geographic regions.
Publications
- (2014) Apicidin F: Characterization and Genetic Manipulation of a New Secondary Metabolite Gene Cluster in the Rice Pathogen Fusarium fujikuroi. PLoS One, 24; 9(7):e103336
Niehaus EM, Janevska S, von Bargen KW, Sieber CM, Harrer H, Humpf HU, Tudzynski B
(See online at https://doi.org/10.1371/journal.pone.0103336) - (2014) Characterization of the fusaric acid gene cluster in Fusarium fujikuroi. Appl. Microbiol. Biotechnol. 98: 1749–1762
Niehaus, E.M., von Bargen, K., Espino, J.J., Pfannmüller, A., Humpf, H.-U., Tudzynski, B
(See online at https://doi.org/10.1007/s00253-013-5453-1) - (2014) Fusarins and Fusaric Acid in Fusaria. In: Biosynthesis and Molecular Genetics of Fungal Secondary Metabolites. Series “Fungal Biology”; Martín, J.-F., García-Estrada, C., Zeilinger, S. (Eds.); Springer New York 2014
Niehaus EM, Díaz-Sánchez, V., von Bargen, K., Kleigrewe,K., Humpf, H-U., Limón, MC, and Tudzynski, B.
(See online at https://doi.org/10.1007/978-1-4939-1191-2_11) - (2015) Genetic engineering, high resolution mass spectrometry and nuclear magnetic resonance spectroscopy elucidate the bikaverin biosynthetic pathway in Fusarium fujikuroi. Fungal Genet Biol. 84:26-36
Arndt B, Studt L, Wiemann P, Osmanov H, Kleigrewe K, Köhler J, Krug I, Tudzynski B, Humpf HU
(See online at https://doi.org/10.1016/j.fgb.2015.09.006) - (2015) Isolation and Structure Elucidation of the Products of the PKS19 Gene Cluster in Fusarium fujikuroi. J. Natural Products 78(8):1809-1815
von Bargen, K., Niehaus EM, Krug, I., Bergander, K., Würthwein, E-U., Humpf, H-U., Tudzynski, B.
(See online at https://doi.org/10.1021/np5008137) - (2016) Gibepyrone biosynthesis in the rice pathogen Fusarium fujikuroi is facilitated by a small polyketide synthase gene cluster. J Biol Chem 291(53):27403-27420
Janevska S, Arndt B, Niehaus EM, Burkhardt I, Rösler SM, Brock NL, Humpf HU, Dickschat JS, Tudzynski B
(See online at https://doi.org/10.1074/jbc.M116.753053) - (2016) Gibepyrone biosynthesis in the rice pathogen Fusarium fujikuroi is facilitated by a small polyketide synthase gene cluster. J Biol Chem 291(53):27403-27420
Janevska S, Arndt B, Niehaus EM, Burkhardt I, Rösler SM, Brock NL, Humpf HU, Dickschat JS, Tudzynski B
(See online at https://doi.org/10.1074/jbc.M116.753053) - (2016) Sound of silence: The beauvericin cluster in Fusarium fujikuroi is controlled by cluster-specific and global regulators mediated by H3K27 modification. Environ Microbiol.18: 4282-4302
Niehaus EM, Studt L, von Bargen KW, Kummer W, Humpf HU, Reuter G, Tudzynski B
(See online at https://doi.org/10.1111/1462-2920.13576) - (2017) A fungal N- dimethylallyltryptophan metabolite from Fusarium fujikuroi. ChemBioChem. 18(10):899-904
Arndt B, Janevska S, Schmid R, Hübner F, Tudzynski B, Humpf HU
(See online at https://doi.org/10.1002/cbic.201600691) - (2017) Establishment of the Inducible Tet-On System for the activation of the Silent Trichosetin Gene Cluster in Fusarium fujikuroi. Toxins. 9(4)
Janevska S, Arndt B, Baumann L, Apken LH, Maciel Mauriz Marques L, Humpf HU, Tudzynski B
(See online at https://doi.org/10.3390/toxins9040126) - (2017) The GATA-Type transcription factor Csm1 regulates conidiation and secondary metabolism in Fusarium fujikuroi. Front. Microbiol. 8:1175
Niehaus E-M, Schumacher J, Burkhardt I, Rabe P, Münsterkötter M, Güldener U, Sieber CMK, Dickschat JS and Tudzynski B
(See online at https://doi.org/10.3389/fmicb.2017.01175)
