초록
<P>Actinomycetes and filamentous fungi produce a wide range of bioactive compounds, with applications as antimicrobials, anticancer agents or agrochemicals. Their genomes contain a far larger number of gene clusters for natural products than originally anticipated, and novel approaches are required to exploit this potential reservoir of new drugs. Here, we show that co-cultivation of the filamentous model microbes <I>Streptomyces coelicolor</I> and <I>Aspergillus niger</I> has a major impact on their secondary metabolism. NMR-based metabolomics combined with multivariate data analysis revealed several compounds that correlated specifically to co-cultures, including the cyclic dipeptide cyclo(Phe-Phe) and 2-hydroxyphenylacetic acid, both of which were produced by <I>A. niger</I> in response to <I>S. coelicolor</I>. Furthermore, biotransformation studies with <I>o</I>-coumaric acid and caffeic acid resulted in the production of the novel compounds (<I>E</I>)-2-(3-hydroxyprop-1-en-1-yl)-phenol and (2<I>E</I>,4<I>E</I>)-3-(2-carboxy-1-hydroxyethyl)-2,4-hexadienedioxic acid, respectively. This highlights the utility of microbial co-cultivation combined with NMR-based metabolomics as an efficient pipeline for the discovery of novel natural products.</P>