Epoxinnamide: An Epoxy Cinnamoyl-Containing Nonribosomal Peptide from an Intertidal Mudflat-Derived Streptomyces sp.
- 주제(키워드) cinnamoyl-containing nonribosomal peptide , Streptomyces , biosynthetic gene cluster , bifunctional thioesterase , quinone reductase , angiogenesis
- 주제(기타) Chemistry, Medicinal; Pharmacology & Pharmacy
- 설명문(일반) [Kang, Sangwook; Han, Jaeho; Jang, Sung Chul; An, Joon Soo; Shim, Sang Hee; Lee, Sang Kook; Oh, Dong-Chan] Seoul Natl Univ, Coll Pharm, Nat Prod Res Inst, Seoul 08826, South Korea; [Kang, Ilnam; Cho, Jang-Cheon] Inha Univ, Dept Biol Sci, Incheon 22212, South Korea; [Kwon, Yun] Kyungpook Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Daegu 41566, South Korea; [Nam, Sang-Jip] Ewha Womans Univ, Dept Chem & Nanosci, Seoul 03760, South Korea
- 등재 SCIE, SCOPUS
- OA유형 Green Published, gold
- 발행기관 MDPI
- 발행년도 2022
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000202922
- 본문언어 영어
- Published As https://doi.org/10.3390/md20070455
- PubMed https://pubmed.ncbi.nlm.nih.gov/35877748
초록/요약
Cinnamoyl-containing nonribosomal peptides (CCNPs) form a unique family of actinobacterial secondary metabolites and display various biological activities. A new CCNP named epoxinnamide (1) was discovered from intertidal mudflat-derived Streptomyces sp. OID44. The structure of 1 was determined by the analysis of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) data along with a mass spectrum. The absolute configuration of 1 was assigned by the combination of advanced Marfey's method, (3)J(HH) and rotating-frame overhauser effect spectroscopy (ROESY) analysis, DP4 calculation, and genomic analysis. The putative biosynthetic pathway of epoxinnamide (1) was identified through the whole-genome sequencing of Streptomyces sp. OID44. In particular, the thioesterase domain in the nonribosomal peptide synthetase (NRPS) biosynthetic gene cluster was proposed as a bifunctional enzyme, which catalyzes both epimerization and macrocyclization. Epoxinnamide (1) induced quinone reductase (QR) activity in murine Hepa-1c1c7 cells by 1.6-fold at 5 mu M. It also exhibited effective antiangiogenesis activity in human umbilical vein endothelial cells (IC50 = 13.4 mu M).
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