Phylogenomic Identification of a Highly Conserved Copper-Binding RiPP Biosynthetic Gene Cluster in Marine <i>Microbulbifer</i> Bacteria
Conserved biosynthetic gene clusters (BGCs) are often tied to the production of natural products that perform critical functions in an organism's physiology and ecological interactions. Here, by phylogenetic analysis across the bacterial genus, we report the obligate conservation of a BGC in genomes of cosmopolitan marine <i>Microbulbifer</i> bacteria. This genus is a common member of marine microbiomes, and this BGC was conserved in <i>Microbulbifer</i> genomes regardless of phylogenetic or geographical dispersal. The post-translationally modified peptidic product encoded by this BGC─which was accessed via heterologous production and its structure elucidated using a combination of mass spectrometry and NMR spectroscopy─was found to be a copper chelator. Similar BGCs were then found in genomes of other marine bacterial genera coinhabiting the microbiomes of sponges and corals. The phylogenomic workflows described herein were implemented in a pedagogic setting at the Georgia Institute of Technology to provide hands-on instruction to undergraduate students in bacterial phylogeny, genome mining, and natural product chemistry.
Authors
- Richard J. Thompson (ORCID: https://orcid.org/0000-0001-5652-0150)
- Elaine Wang (ORCID: https://orcid.org/0000-0003-1326-1421)
- Paige Mandelare-Ruiz
- Michelle Han (ORCID: https://orcid.org/0000-0003-2812-6193)
- Alan B. Hollingsworth (ORCID: https://orcid.org/0000-0002-7856-6798)
- Valerie Jean Paul (ORCID: https://orcid.org/0000-0002-4691-1569)
- C. Kirby
- Ronghu Wu (ORCID: https://orcid.org/0000-0001-9493-9462)
- Longhai Fu
- Fang Ou (ORCID: https://orcid.org/0000-0002-5037-0857)
- Aaron B. Ingham (ORCID: https://orcid.org/0000-0001-8006-9443)
- Weimao Zhong (ORCID: https://orcid.org/0000-0002-1358-4944)
- Anastasiia Kostenko
- Vinayak Agarwal (ORCID: https://orcid.org/0000-0002-2517-589X)
- William H. Yang
- Jason R. Stokes (ORCID: https://orcid.org/0000-0001-7784-9297)
- Éric Oswald (ORCID: https://orcid.org/0000-0002-3017-0081)
- Allegra T. Aron (ORCID: https://orcid.org/0000-0002-9596-021X)
- Gregory J. Anderson (ORCID: https://orcid.org/0000-0002-8814-5866)
- Alison E. Onstine
- Benjamin Edmonds (ORCID: https://orcid.org/0000-0002-8872-6951)
- F. N. U. Vidya
- Yifan Tang (ORCID: https://orcid.org/0000-0002-2528-0657)
- Emmanuel Asante (ORCID: https://orcid.org/0000-0001-8917-7360)
- C. Mack
- T. So
- Alice Landrum
- Nikki S. Nobari
- Cecilia L. Polevoy
- Yasmin Sharifian
- Rishabh Vuthamaraju
- Tamilore T. Adeogun
Institutions
- Georgia Institute of Technology (US)
- University of Denver (US)
- Smithsonian Marine Station (US)
Publication Details
- Journal
- ACS Chemical Biology
- Published
- 2025-09-19
- DOI
- https://doi.org/10.1021/acschembio.5c00507
- Citations
- 6
- Primary Topic
- Genomics and Phylogenetic Studies
- Type
- article
- Field-Weighted Citation Impact
- 4.84