Phosphonate natural products are a unique yet largely underexplored class of bioactive metabolites with considerable pharmaceutical and biotechnological potential. By combining genome mining with experimental validation, researchers at DSMZ and their collaborators uncovered numerous previously unrecognized phosphonate producers and and confirmed their phosphonate-producing capacity.
In this study, 940 genome sequenced actinomycete strains from the DSMZ and University of Tübingen collections were screened for phosphonate biosynthetic gene clusters using the conserved pepM gene as a molecular marker. This genome mining approach identified 54 candidate phosphonate producing strains, most of which had not been linked to phosphonate production before. Functional evaluation via phosphonate specific bioassays and 31P NMR spectroscopy confirmed phosphonate production in 21 strains, highlighting the effectiveness of combining genome-based prioritization with targeted analytical methods.
Among these strains, the rare actinomycete Kitasatospora fiedleri DSM 114396ᵀ represents one example harboring a unique phosphonate biosynthetic gene cluster. Genetic deletion of the conserved pepM gene abolished phosphonate production, confirming pathway functionality, whereas overexpression of a cluster-situated LuxR-like regulator significantly enhanced phosphonate production, demonstrating a tractable regulatory handle for pathway activation and yield improvement.
Overall, the work highlights actinomycetes as a rich genomic reservoir for novel phosphonate natural products and underscores the value of curated microbial collections by establishing an effective integrated workflow for phosphonate discovery.
Original publication
Expanding the actinomycetes landscape for phosphonate natural products through genome mining.
Zimmermann, A., Xia, S.N., Moschny, J., Gomez-Escribano, J.P., Boldt, J., Nübel, U., Nouioui, I, Krause, J., Irle, M.K., Metcalf, W.W., Hughes, C.C., Mast, Y. RSC Chem Biol. 2025 Dec 16. doi: 10.1039/d5cb00254k
DSMZ contact: Prof. Dr. Yvonne Mast
