Azetidine-Bearing Non-Ribosomal Peptides, Bonnevillamides D and E, Isolated from a Carrion Beetle-Associated Actinomycete

Yern Hyerk Shin, Yeon Hee Ban, Jisu Shin, In Wook Park, Soljee Yoon, Keebeom Ko, Jongheon Shin, Sang Jip Nam, Jaclyn M. Winter, Youngsoo Kim, Yeo Joon Yoon, Dong Chan Oh

Research output: Contribution to journalArticlepeer-review

Abstract

Two new nonribosomal peptides, bonnevillamides D and E (1 and 2), have been discovered in Streptomyces sp. UTZ13 isolated from the carrion beetle, Nicrophorus concolor. Combinational analysis of the UV, MS, and NMR spectroscopic data revealed that their planar structures were comprised of dichlorinated linear peptides containing nonproteinogenic amino acid residues, such as 4-methylazetidinecarboxylic acid and 4-O-acetyl-5-methylproline. The configurations of bonnevillamides D and E (1 and 2) were determined based on ROESY correlations, the advanced Marfey's method, phenylglycine methyl ester derivatization, molecular modeling, and circular dichroism spectroscopy. The nonribosomal peptide synthetase biosynthetic pathway of bonnevillamides D and E has been proposed using bioinformatic analysis of the whole-genome sequence data of Streptomyces sp. UTZ13. Their biological activity toward the aggregation of amyloid-β, which is one of the key pathogenic proteins in Alzheimer's disease, was evaluated using a thioflavin T assay and gel electrophoresis. Bonnevillamides D and E reversed the fibril formation by inducing the monomerization of amyloid-β aggregates.

Original languageEnglish
Pages (from-to)11149-11159
Number of pages11
JournalJournal of Organic Chemistry
Volume86
Issue number16
DOIs
Publication statusAccepted/In press - 2021

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea grants funded by the Korean Government (Ministry of Science and ICT) (2021R1A4A2001251, 2019R1A2B5B03069338, and 2020R1A2C2003518) and the Gordon and Betty Moore Foundation (GBMF7621, 10.37807/GBMF7621 ) to J.M.W.

Publisher Copyright:
© 2021 American Chemical Society. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

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