Azetidine-Bearing Non-Ribosomal Peptides, Bonnevillamides D and E, Isolated from a Carrion Beetle-Associated Actinomycete
- 주제(기타) Chemistry, Organic
- 설명문(일반) [Shin, Yern-Hyerk; Ban, Yeon Hee; Ko, Keebeom; Shin, Jongheon; Yoon, Yeo Joon; Oh, Dong-Chan] Seoul Natl Univ, Coll Pharm, Nat Prod Res Inst, Seoul 08826, South Korea; [Shin, Jisu; Park, In Wook; Yoon, Soljee; Kim, YoungSoo] Yonsei Univ, Dept Pharm, Yonsei Inst Pharmaceut Sci, Incheon 21983, South Korea; [Shin, Jisu; Park, In Wook; Yoon, Soljee; Kim, YoungSoo] Yonsei Univ, Dept Integrat Biotechnol & Translat Med, Incheon 21983, South Korea; [Nam, Sang-Jip] Ewha Womans Univ, Dept Chem & Nanosci, Seoul 03760, South Korea; [Winter, Jaclyn M.] Univ Utah, Dept Med Chem, Salt Lake City, UT 84112 USA
- 등재 SCIE, SCOPUS
- 발행기관 AMER CHEMICAL SOC
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000183463
- 본문언어 영어
- Published As http://dx.doi.org/10.1021/acs.joc.1c00360
초록/요약
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-beta, 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-beta aggregates.
more