Prediction of secondary metabolite encoding genes based on chemical structure analysis
Makaleler > Tam Makale · 2016
Yazarlar: Isbrandt T, Nielsen M, Hoeck C, Yüksel GEZGİN, Frandsen R, Nielsen KF, Ostenfeld Larsen T
Planta Medica, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2016, cilt 81, ss S1-S381
Özet
Dereplication of the secondary metabolite profile from the filamentous fungus Aspergillus brasiliensis , by High Performance Liquid Chromatography coupled with Diode Array Detection and High Resolution Mass Spectrometry, [1] lead to the discovery of a novel biomarker having a unique UV spectrum and elemental composition. Structural elucidation based on Nuclear Magnetic Resonance spectroscopy of the pure compound revealed an apolar polyketide or fatty acid derived secondary metabolite, possibly assembled from two entities, a C8 and a C12 chain, fused via a Claisen-like condensation and subsequent cyclisation to form a core lactone ring structure. The compound has been named brasenol. To our knowledge, only two other compunds contain a similar ring structure; namely alternaric acid from Alternaria solani and fujikurin D found in Fusarium fujikuroi [2,3]. Despite the apolar nature of the compound initial bioassay investigation have demonstrated antibacterial activity (MIC = 28.44 µg/mL) against methicillin-resistant Staphylococcus aureus MB5393. We are currently investigating whether other closely related black Aspergilli in section nigri could also be identified as brasenol producers. This will be followed by comparative bioinformatics analysis of their already sequenced genomes, setting the scene for construction of knock out mutants of potential candidate genes involved using CRISPR/Cas9 in A. brasiliensis [4]. This poster will summarize our efforts towards characterization of the biosynthetic pathway of this new compound. Fig. 2: Structure of brasenol. Acknowledgements: We thank Fundación Medina, Granada, Spain for bioactivity assessment.