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Metagenomic study of lake microbial mats reveals protease-inhibiting antiviral peptides from a core microbiome member.

Authors :
Padhi C
Field CM
Forneris CC
Olszewski D
Fraley AE
Sandu I
Scott TA
Farnung J
Ruscheweyh HJ
Narayan Panda A
Oxenius A
Greber UF
Bode JW
Sunagawa S
Raina V
Suar M
Piel J
Source :
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Dec 03; Vol. 121 (49), pp. e2409026121. Date of Electronic Publication: 2024 Nov 25.
Publication Year :
2024

Abstract

In contrast to the large body of work on bioactive natural products from individually cultivated bacteria, the chemistry of environmental microbial communities remains largely elusive. Here, we present a comprehensive bioinformatic and functional study on a complex and interaction-rich ecosystem, algal-bacterial (microbial) mats of Lake Chilika in India, Asia's largest brackish water body. We report the bacterial compositional dynamics over the mat life cycle, >1,300 reconstructed environmental genomes harboring >2,200 biosynthetic gene clusters (BGCs), the successful cultivation of a widespread core microbiome member belonging to the genus Rheinheimera , heterologous reconstitution of two silent Rheinheimera biosynthetic pathways, and new compounds with potent protease inhibitory and antiviral activities. The identified substances, posttranslationally modified peptides from the graspetide and spliceotide families, were targeted among the large BGC diversity by applying a strategy focusing on recurring multi-BGC loci identified in diverse samples, suggesting their presence in successful colonizers. In addition to providing broad insights into the biosynthetic potential of a poorly studied community from sampling to bioactive substances, the study highlights the potential of ribosomally synthesized and posttranslationally modified peptides as a large, underexplored resource for antiviral drug discovery.<br />Competing Interests: Competing interests statement:The authors declare no competing interest.

Details

Language :
English
ISSN :
1091-6490
Volume :
121
Issue :
49
Database :
MEDLINE
Journal :
Proceedings of the National Academy of Sciences of the United States of America
Publication Type :
Academic Journal
Accession number :
39585984
Full Text :
https://doi.org/10.1073/pnas.2409026121