title: Family-wide Structural Characterization and Genomic Comparisons Decode the Diversity-oriented Biosynthesis of Thalassospiramides by Marine Proteobacteria.
abstract: The thalassospiramide lipopeptides have great potential for therapeutic applications; however, their structural and functional diversity and biosynthesis are poorly understood. Here, by cultivating 130 Rhodospirillaceae strains sampled from oceans worldwide, we discovered 21 new thalassospiramide analogues and demonstrated their neuroprotective effects. To investigate the diversity of biosynthetic gene cluster (BGC) architectures, we sequenced the draft genomes of 28 Rhodospirillaceae strains. Our family-wide genomic analysis revealed three types of dysfunctional BGCs and four functional BGCs whose architectures correspond to four production patterns. This correlation allowed us to reassess the "diversity-oriented biosynthesis" proposed for the microbial production of thalassospiramides, which involves iteration of several key modules. Preliminary evolutionary investigation suggested that the functional BGCs could have arisen through module/domain loss, whereas the dysfunctional BGCs arose through horizontal gene transfer. Further comparative genomics indicated that thalassospiramide production is likely to be attendant on particular genes/pathways for amino acid metabolism, signaling transduction, and compound efflux. Our findings provide a systematic understanding of thalassospiramide production and new insights into the underlying mechanism.
authors.affiliation: From the Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong.
authors.forename: Weipeng
authors.initials: W
authors.lastname: Zhang
authors.affiliation: From the Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong.
authors.forename: Liang
authors.initials: L
authors.lastname: Lu
authors.affiliation: the Third Institute of Oceanography, State Oceanic Administration, Xiamen 361000, China.
authors.forename: Qiliang
authors.initials: Q
authors.lastname: Lai
authors.affiliation: From the Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong.
authors.forename: Beika
authors.initials: B
authors.lastname: Zhu
authors.affiliation: From the Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong.
authors.forename: Zhongrui
authors.initials: Z
authors.lastname: Li
authors.affiliation: the School of Life Science, Shenzhen University, Shenzhen, Guangdong Province 518060, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: the Third Institute of Oceanography, State Oceanic Administration, Xiamen 361000, China.
authors.forename: Zongze
authors.initials: Z
authors.lastname: Shao
authors.affiliation: From the Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong.
authors.forename: Karl
authors.initials: K
authors.lastname: Herrup
authors.affiliation: the Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California 92037, and.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Moore
authors.affiliation: the Department of Chemistry, Queen's University, Kingston, Ontario K7L 3N6, Canada avena.ross@queensu.ca.
authors.forename: Avena C
authors.initials: AC
authors.lastname: Ross
authors.affiliation: From the Division of Life Science, Hong Kong University of Science and Technology, Kowloon, Hong Kong, boqianpy@ust.hk.
authors.forename: Pei-Yuan
authors.initials: PY
authors.lastname: Qian
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D023281:Genomics / Q000379:methods*; D008386:Marine Biology; D051379:Mice; D008810:Mice, Inbred C57BL; D005810:Multigene Family / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010802:Phylogeny; D020560:Proteobacteria / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D018696:Neuroprotective Agents; D010456:Peptides, Cyclic; C520245:thalassospiramide A; C520244:thalassospiramide B
keywords: bacteria; biosynthesis; genomics; natural product; neuroprotection