New bioactive compounds from Fusarium fujikuroi

In the field of natural products, moulds provide a large spectrum of bioactive compounds and are therefore important targets to analyse. One of these moulds is Fusarium fujikuroi, a rice pathogen causing the foolish seedling disease due to its secretion of the secondary metabolites gibberellic acids, a group of highly bioactive phytohormones [1]. Besides these isoprenoids, it produces a broad range of other interesting compounds, e.g. the cyclic tetrapeptide apicidin F which shows antimalarial activity [2]. The genome of F. fujikuroi was fully sequenced, revealing the presence of altogether 47 putative secondary metabolite gene clusters, most without yet assigned product [3]. Besides, global regulatory genes that encode positive or negative regulators of secondary metabolite gene clusters are under investigation. With the help of genetic engineering, overexpression and deletion mutants of biosynthetic genes and/or global regulator genes were generated. In this study, we present several identified metabolites, including the products of a dimethylallyl tryptophan synthase, a polyketide synthase (PKS) and a PKS-non ribosomal peptide hybrid (see Fig. 1). Those were identified by HPLC-UV-HRMS measurements of the created mutants in comparison to the wild type. To enhance the identification process, the secondary metabolite profiles were analysed with the software tool MZmine 2 [4], resulting in the identification of new or missing peaks, respectively. The compounds were isolated by different methods and their structures were elucidated in detail by NMR and HPLC-HRMS. With this procedure, known secondary metabolites [5,6] as well as new, yet unknown compounds were identified, and corresponding gene clusters characterized [7].

Fig. 1: Structures of compounds presented in the study.

Acknowledgements: Financial support by the DFG (Project HU 730/9 – 3) and the NRW Graduate School of Chemistry is gratefully acknowledged.

Keywords: Fusarium, Genomics, Bikaverin, Biosynthesis, Natural Products, Mass spectrometry, NMR spectroscopy.

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