Please use this identifier to cite or link to this item: doi:10.22028/D291-41690
Title: Unusual peptide-binding proteins guide pyrroloindoline alkaloid formation in crocagin biosynthesis
Author(s): Adam, Sebastian
Zheng, Dazhong
Klein, Andreas
Volz, Carsten
Mullen, William
Shirran, Sally L.
Smith, Brian O.
Kalinina, Olga V.
Müller, Rolf
Koehnke, Jesko
Language: English
Title: Nature Chemistry
Volume: 15
Issue: 4
Pages: 560-568
Publisher/Platform: Springer Nature
Year of Publication: 2023
Free key words: Peptides
X-ray crystallography
DDC notations: 500 Science
Publikation type: Journal Article
Abstract: Ribosomally synthesized and post-translationally modifed peptide natural products have provided many highly unusual scafolds. This includes the intriguing alkaloids crocagins, which possess a tetracyclic core structure and whose biosynthesis has remained enigmatic. Here we use in vitro experiments to demonstrate that three proteins, CgnB, CgnC and CgnE, are sufcient for the production of the hallmark tetracyclic crocagin core from the precursor peptide CgnA. The crystal structures of the homologues CgnB and CgnE reveal them to be the founding members of a peptide-binding protein family and allow us to rationalize their distinct functions. We further show that the hydrolase CgnD liberates the crocagin core scafold, which is subsequently N-methylated by CgnL. These insights allow us to propose a biosynthetic scheme for crocagins. Bioinformatic analyses based on these data led to the discovery of related biosynthetic pathways that may provide access to a structurally diverse family of peptide-derived pyrroloindoline alkaloids.
DOI of the first publication: 10.1038/s41557-023-01153-w
URL of the first publication:
Link to this record: urn:nbn:de:bsz:291--ds-416903
ISSN: 1755-4349
Date of registration: 1-Mar-2024
Description of the related object: Supplementary information
Related object:
Faculty: M - Medizinische Fakultät
NT - Naturwissenschaftlich- Technische Fakultät
Department: M - Medizinische Biometrie, Epidemiologie und medizinische Informatik
NT - Pharmazie
Professorship: M - Prof. Dr. Olga Kalinina
NT - Prof. Dr. Rolf Müller
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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