In natural product research, the search of new sources of compounds is a key element. In this respect microorganisms have provided a large number of biologically active molecules [1]. Recently, the use of fungal co-culture for the induction of new natural products has emerged as a new field in drug discovery [2]. A key point for the success of such studies is the development of co-culture experiments that provide high reproducibility of metabolite induction pattern and that are compatible with high throughput analytical procedure for the screening of a large number of mono-colture and co-culture samples and further data mining. To tackle this issue, a method based on 12-well plate miniaturized Petri dishes compatible with high throughput UHPLC-TOF-MS metabolomics [3] has been developed. Various culture condition parameters were optimized for fungal growth such as culture medium volume and culture duration. This strategy was used to screen for metabolite induction and study their dynamics in the co-cultures of soil fungus Aspergillus clavatus and a systemic human pathogenic fungus Fusarium sp. This approach provided a satisfactory reproducibility and was used for the identification of induced biomarkers. This study demonstrates the consistent induction of new metabolites through co-culture. Moreover, upscaling of the co-cultures conditions to large Petri dishes shows that the main induced metabolites were also produced allowing their purification for further de novo identification and evaluation of their bioactivity. Acknowledgements: This work was supported by Swiss National Science Foundation Sinergia Grant CRSII3_127187 (to J.-L. W., K. G. and M. M.). [1] Berdy J, J. Antibiot. 2005, 58, 1. [2] Glauser G et al., J. Agr. Food. Chem., 2009, 57, 1127. [3] Bertrand S et al., J. Chromatography A , in press , 2013
