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A Bifunctional Leader Peptidase/ABC Transporter Protein Is Involved in the Maturation of the Lasso Peptide Cochonodin I from Streptococcus suis.

ABSTRACT: Lasso peptides are members of the natural product superfamily of ribosomally synthesized and post-translationally modified peptides (RiPPs). Here, we describe the first lasso peptide originating from a biosynthetic gene cluster belonging to a unique lasso peptide subclade defined by the presence of a bifunctional protein harboring both a leader peptidase (B2) and an ABC transporter (D) domain. Bioinformatic analysis revealed that these clusters also encode homologues of the NisR/NisK regulatory system and the NisF/NisE/NisG immunity factors, which are usually associated with the clusters of antimicrobial class I lanthipeptides, such as nisin, another distinct RiPP subfamily. The cluster enabling the heterologous production of the lasso peptide cochonodin I in E. coli originated from Streptococcus suis LSS65, and the threaded structure of cochonodin I was evidenced through extensive MS/MS analysis and stability assays. It was shown that the ABC transporter domain from SsuB2/D is not essential for lasso peptide maturation. By extensive genome mining dedicated exclusively to other lasso peptide biosynthetic gene clusters featuring bifunctional B2/D proteins, it was furthermore revealed that many bacteria associated with human or animal microbiota hold the biosynthetic potential to produce cochonodin-like lasso peptides, implying that these natural products might play roles in human and animal health.

SUBMITTER: Hegemann JD

PROVIDER: S-EPMC9390802 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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A Bifunctional Leader Peptidase/ABC Transporter Protein Is Involved in the Maturation of the Lasso Peptide Cochonodin I from <i>Streptococcus</i> <i>suis</i>.

Hegemann Julian D JD Jeanne Dit Fouque Kevin K Santos-Fernandez Miguel M Fernandez-Lima Francisco F

Journal of natural products 20211001 10

Lasso peptides are members of the natural product superfamily of ribosomally synthesized and post-translationally modified peptides (RiPPs). Here, we describe the first lasso peptide originating from a biosynthetic gene cluster belonging to a unique lasso peptide subclade defined by the presence of a bifunctional protein harboring both a leader peptidase (B2) and an ABC transporter (D) domain. Bioinformatic analysis revealed that these clusters also encode homologues of the NisR/NisK regulatory ...[more]

PMID: 34597519

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Dataset Information

A Bifunctional Leader Peptidase/ABC Transporter Protein Is Involved in the Maturation of the Lasso Peptide Cochonodin I from Streptococcus suis.

Publications

A Bifunctional Leader Peptidase/ABC Transporter Protein Is Involved in the Maturation of the Lasso Peptide Cochonodin I from <i>Streptococcus</i> <i>suis</i>.

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