Natural products from underexplored pathways and extreme environments
Our Research
Natural products exhibit versatile bioactivities and provide valuable lead structures for drug discovery. Although the total number of characterized natural products increased over the last decades, only few of the compounds discovered had previously unknown chemical structures. However, structurally new chemicals are urgently required for the development of antibiotics with resistance-breaking properties and other active drugs. Recent advances in the field of natural product discovery indicate that there are several promising avenues to detect bioactive natural products with new chemical entities. The wealth of publicly available (meta)genomes conceals significant biosynthetic potential that has yet to be elucidated. In addition, there is an increasing number of talented microbial natural product producers that have been isolated but remain underexplored. Moreover, the isolation of natural products from habitats and organisms thought to lack the potential for natural product biosynthesis (e.g. hot sulfur springs) further supports the hypothesis that the known natural product chemical space covers only the tip of the iceberg.
The Hubrich Lab aims to contribute to the expansion of the currently known natural product chemical diversity and to characterize the biosynthetic enzymes involved. The resulting compounds and enzymes will be used to develop and improve anti-infectives through bioengineering. To achieve this goal, metabolic pathways of talented but neglected natural product producers such as cyanobacteria and microbes that colonize extreme habitats will be investigated. The research approach applies interdisciplinary methods of modern natural product research and chemical biology, including bioinformatics, molecular and synthetic biology, microbiology, enzymology and (bio)synthetic chemistry.
Our Research
Natural products exhibit versatile bioactivities and provide valuable lead structures for drug discovery. Although the total number of characterized natural products increased over the last decades, only few of the compounds discovered had previously unknown chemical structures. However, structurally new chemicals are urgently required for the development of antibiotics with resistance-breaking properties and other active drugs. Recent advances in the field of natural product discovery indicate that there are several promising avenues to detect bioactive natural products with new chemical entities. The wealth of publicly available (meta)genomes conceals significant biosynthetic potential that has yet to be elucidated. In addition, there is an increasing number of talented microbial natural product producers that have been isolated but remain underexplored. Moreover, the isolation of natural products from habitats and organisms thought to lack the potential for natural product biosynthesis (e.g. hot sulfur springs) further supports the hypothesis that the known natural product chemical space covers only the tip of the iceberg.
The Hubrich Lab aims to contribute to the expansion of the currently known natural product chemical diversity and to characterize the biosynthetic enzymes involved. The resulting compounds and enzymes will be used to develop and improve anti-infectives through bioengineering. To achieve this goal, metabolic pathways of talented but neglected natural product producers such as cyanobacteria and microbes that colonize extreme habitats will be investigated. The research approach applies interdisciplinary methods of modern natural product research and chemical biology, including bioinformatics, molecular and synthetic biology, microbiology, enzymology and (bio)synthetic chemistry.
“New chemical entities are urgently needed to tackle antibiotic resistance. We focus on underexplored pathways and extreme habitats to discover true structural novelty and harness them for the bioengineering of potent anti-infectives.”
Florian Hubrich studied chemistry and biology at the University of Freiburg. Following his Staatsexamen, he started a PhD in chemical biology supervised by Jennifer Andexer and Michael Müller at the Institute of Pharmaceutical Sciences in Freiburg and graduated at the end of 2014. Afterwards, Florian Hubrich moved to Switzerland and worked for the Bachem AG, a world leading company for peptide drug manufacturing, as project chemist for analytical method development and group leader for in-process control. In 2019, he returned to academia and joined Jörn Piel’s lab as a postdoctoral researcher at the ETH Zurich. For his postdoctoral research, he studied the biosynthesis of ribosomally synthesized and post-translational modified peptides (RiPPs). In 2024, Hubrich started his junior research group at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) and the Saarland University.
Florian Hubrich’s research interest is the expansion of the natural product chemical space at the interface of primary and secondary metabolism. His group will focus on the bioengineering of antimicrobial lipopeptides to understand the effect of distinct lipid moieties on bioactivity and therapeutic properties.
Selected Publications
L. Paoli, H.-J. Ruscheweyh*, C. C. Forneris*, F. Hubrich*, S. Kautsar, Q. Clayssen, A. Bhushan, G. Salazar, A. Milanese, D. Gehrig, A. Lotti, M. Larralde, L. M. Carroll, P. Sánchez, A. A. Zayed, D. R. Cronin, S. G. Acinas, P. Bork, C. Bowler, T. O. Delmont, M. B. Sullivan, P. Wincker, G. Zeller, S. L. Robinson, J. Piel and S. Sunagawa, Biosynthetic potential of the global ocean microbiome. Nature, 2022, 607, 111–118. doi: 10.1038/s41586-022-04862-3
*equal contribution
F. Hubrich*, N. M. Bösch*, C. Chepkirui, B. I. Morinaka, M. Rust, M. Gugger, S. L. Robinson, A. L. Vagstad and J. Piel, Ribosomally derived lipopeptides containing distinct fatty acyl moieties. Proc. Natl. Acad. Sci. U.S.A., 2022, 119, e2113120119. doi: 10.1073/pnas.2113120119
*equal contribution
F. Hubrich§, M. Müller and J. N. Andexer§, Chorismate and isochorismate converting enzymes: versatile catalysts acting on an important metabolic node. Chem. Commun. (Camb.), 2021, 57, 2441–2463. doi: 10.1039/D0CC08078K
§corresponding authors
F. Hubrich, P. Juneja, K. Diederichs, M. Müller, W. Welte and J. N. Andexer, Chorismatase mechanisms reveal fundamentally different types of reaction in a single conserved protein fold. J. Am. Chem. Soc., 2015, 137, 11032–11037. doi: 10.1021/jacs.5b05559
Highlighted in J. Am. Chem. Soc.
F. Hubrich, M. Müller and J. N. Andexer, In vitro production and purification of isochorismate using a two-enzyme cascade. J. Biotechnol., 2014, 191, 93–98. doi: 10.1016/j.jbiotec.2014.06.003
