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Discovery and Biosynthesis of Ureidopeptide Natural Products Macrocyclized via Indole N-acylation in Marine Microbulbifer spp. Bacteria |
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| Authors: | Dr Weimao Zhong Jessica M Deutsch Dongqi Yi Nadine H Abrahamse Ipsita Mohanty Samuel G Moore Prof?Dr Andrew C McShan Prof?Dr Neha Garg Prof?Dr Vinayak Agarwal |
| Affiliation: | 1. School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA, 30332 USA
These authors contributed equally to this work.;2. School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA, 30332 USA;3. School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA, 30332 USA Present Address: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA, 92037 USA;4. School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA, 30332 USA Center for Microbial Dynamics and Infections, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, GA, 30332 USA |
| Abstract: | Commensal bacteria associated with marine invertebrates are underappreciated sources of chemically novel natural products. Using mass spectrometry, we had previously detected the presence of peptidic natural products in obligate marine bacteria of the genus Microbulbifer cultured from marine sponges. In this report, the isolation and structural characterization of a panel of ureidohexapeptide natural products, termed the bulbiferamides, from Microbulbifer strains is reported wherein the tryptophan side chain indole participates in a macrocyclizing peptide bond formation. Genome sequencing identifies biosynthetic gene clusters encoding production of the bulbiferamides and implicates the involvement of a thioesterase in the indolic macrocycle formation. The structural diversity and widespread presence of bulbiferamides in commensal microbiomes of marine invertebrates point toward a possible ecological role for these natural products. |
| Keywords: | biosynthesis microbulbifer natural products NRPS ureido peptide |