Short macrocyclic peptides in sponge genomes

• 成果类型: Article
• 署名作者: Lin, Zhenjian; Agarwal, Vinayak; Cong, Ying; Pomponi, Shirley A.; Schmidt, Eric W.
• 署名单位: Utah System of Higher Education; University of Utah; University System of Georgia; Georgia Institute of Technology; University System of Georgia; Georgia Institute of Technology; Harbor Branch Oceanographic Institute Foundation; State University System of Florida; Florida Atlantic University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13509
• DOI: 10.1073/pnas.2314383121
• 发表日期: 2024-03-12
• 关键词: cyclic-peptides; gene prediction; heptapeptides; demospongiae; EVOLUTION; porifera; agents

摘要

Sponges (Porifera) contain many peptide- specialized metabolites with potent biological activities and significant roles in shaping marine ecology. It is well established that symbiotic bacteria produce bioactive sponge peptides, both on the ribosome (RiPPs) and nonribosomally. Here, we demonstrate that sponges themselves also produce many bioactive macrocyclic peptides, such as phakellistatins and related proline-rich macrocyclic peptides (PRMPs). Using the Stylissa carteri sponge transcriptome, methods were developed to find sequences encoding 46 distinct RiPP-type core peptides, of which ten encoded previously identified PRMP sequences. With this basis set, the genome and transcriptome of the sponge Axinella corrugata was interrogated to find 35 PRMP precursor peptides encoding 31 unique core peptide sequences. At least 11 of these produced cyclic peptides that were present in the sponge and could be characterized by mass spectrometry, including stylissamides A - D and seven previously undescribed compounds. Precursor peptides were encoded in the A. corrugata genome, confirming their animal origin. The peptides contained signal peptide sequences and highly repetitive recognition sequence - core peptide elements with up to 25 PRMP copies in a single precursor. In comparison to sponges without PRMPs, PRMP sponges are incredibly enriched in potentially secreted polypeptides, with >23,000 individual signal peptide encoding genes found in a single transcriptome. The similarities between PRMP biosynthetic genes and neuropeptides in terms of their biosynthetic logic suggest a fundamental biology linked to circular peptides, possibly indicating a widespread and underappreciated diversity of signaling peptide post- translational modifications across the animal kingdom.