title: Expanding the chemical space for natural products by Aspergillus-Streptomyces co-cultivation and biotransformation.
abstract: 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 Streptomyces coelicolor and Aspergillus niger 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 A. niger in response to S. coelicolor. Furthermore, biotransformation studies with o-coumaric acid and caffeic acid resulted in the production of the novel compounds (E)-2-(3-hydroxyprop-1-en-1-yl)-phenol and (2E,4E)-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.
authors.affiliation: 1] Molecular Biotechnology, Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, The Netherlands [2] Natural Products Laboratory, Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, The Netherlands.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Wu
authors.affiliation: Molecular Biotechnology, Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, The Netherlands.
authors.forename: Boris
authors.initials: B
authors.lastname: Zacchetti
authors.affiliation: Molecular Biotechnology, Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, The Netherlands.
authors.forename: Arthur F J
authors.initials: AF
authors.lastname: Ram
authors.affiliation: Molecular Biotechnology, Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, The Netherlands.
authors.forename: Gilles P
authors.initials: GP
authors.lastname: van Wezel
authors.affiliation: Molecular Biotechnology, Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, The Netherlands.
authors.forename: Dennis
authors.initials: D
authors.lastname: Claessen
authors.affiliation: Natural Products Laboratory, Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE, The Netherlands.
authors.forename: Young
authors.initials: Y
authors.lastname: Hae Choi
mesh_terms: D001230:Aspergillus / Q000378:metabolism*; D001688:Biological Products / Q000737:chemistry* / Q000378:metabolism*; D001711:Biotransformation; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D066244:Proton Magnetic Resonance Spectroscopy; D013302:Streptomyces / Q000378:metabolism*
chemical_list: D001688:Biological Products