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Multi-species Conserved Sequences02:51

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Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale  studies have provided new insights into the evolutionary relationship between organisms.
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved...
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Short macrocyclic peptides in sponge genomes.

Zhenjian Lin1, Vinayak Agarwal2,3, Ying Cong1

  • 1Department of Medicinal Chemistry, University of Utah, Salt Lake City, UT 84112.

Proceedings of the National Academy of Sciences of the United States of America
|March 5, 2024
PubMed
Summary
This summary is machine-generated.

Sponges produce unique proline-rich macrocyclic peptides (PRMPs), distinct from bacterial ones. This discovery reveals a new class of bioactive compounds with potential roles in animal signaling and post-translational modifications.

Keywords:
RIPPscircular peptidecyclic peptidemetazoan biosynthesissponges

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Area of Science:

  • Marine Biology
  • Biochemistry
  • Genomics

Background:

  • Marine sponges (Porifera) are known sources of bioactive peptides, with symbiotic bacteria traditionally credited for producing many.
  • Ribosomally synthesized and post-translationally modified peptides (RiPPs) and nonribosomal peptides are established classes of sponge-associated metabolites.

Purpose of the Study:

  • To investigate the sponge's own capacity for producing bioactive peptides, specifically proline-rich macrocyclic peptides (PRMPs).
  • To identify and characterize novel PRMPs and their precursor peptides within sponge genomes and transcriptomes.

Main Methods:

  • Bioinformatic analysis of sponge transcriptomes (Stylissa carteri) and genomes (Axinella corrugata) to identify RiPP-type core peptide sequences.
  • Mass spectrometry to characterize cyclic peptides isolated from A. corrugata.
  • Comparative analysis of gene expression in sponges with and without PRMPs.

Main Results:

  • Identification of 46 distinct RiPP-type core peptides from S. carteri, including 10 known PRMPs.
  • Discovery of 35 PRMP precursor peptides in A. corrugata, encoding 31 unique core sequences.
  • Characterization of 11 cyclic peptides from A. corrugata, including novel stylissamides (A-D) and seven undescribed compounds, confirming animal origin.
  • PRMP sponges exhibit a significant enrichment of potentially secreted polypeptides (>23,000 signal peptide genes).

Conclusions:

  • Sponges themselves are significant producers of diverse bioactive macrocyclic peptides, including PRMPs.
  • The biosynthetic logic of PRMPs shares similarities with neuropeptides, suggesting a conserved mechanism for signaling peptide modification across animals.
  • This finding highlights a potentially widespread and underappreciated diversity of animal-derived signaling peptides and post-translational modifications.