2. Academic Validation
  3. Pepticinnamins N, O, and P, Nonribosomal Peptides from the Soil-Derived Streptomyces mirabilis P8-A2

Pepticinnamins N, O, and P, Nonribosomal Peptides from the Soil-Derived Streptomyces mirabilis P8-A2

  • J Nat Prod. 2024 Apr 26;87(4):1075-1083. doi: 10.1021/acs.jnatprod.4c00029.
Manar Magdy Mahmoud Mohamed 1,  Maria Mahmoud Abboud 1,  Matiss Maleckis 1 2,  Luciano D O Souza 3 4,  José M A Moreira 4,  Charlotte H Gotfredsen 5,  Tilmann Weber 2,  Ling Ding 1
Affiliations

Affiliations

  • 1 Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 221, 2800 Kgs. Lyngby, Denmark.
  • 2 The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Søltofts Plads, Building 220, 2800 Kgs. Lyngby, Denmark.
  • 3 Sino-Danish Center for Education and Research, Denmark; Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen, Denmark.
  • 4 Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen, Denmark.
  • 5 Department of Chemistry, Technical University of Denmark, Kemitorvet, Building 207, 2800 Kgs. Lyngby, Denmark.
PMID: 38591246 DOI: 10.1021/acs.jnatprod.4c00029
Abstract

Cinnamoyl moiety containing nonribosomal peptides represented by pepticinnamin E are a growing family of natural products isolated from different Streptomyces species and possess diverse bioactivities. The soil bacterium Streptomyces mirabilis P8-A2 harbors a cryptic pepticinnamin biosynthetic gene cluster, producing azodyrecins as major products. Inactivation of the azodyrecin biosynthetic gene cluster by CRISPR-BEST base editing led to the activation and production of pepticinnamin E (1) and its analogues, pepticinnamins N, O, and P (2-4), the structures of which were determined by detailed NMR spectroscopy, HRMS data, and Marfey's reactions. These new compounds did not show a growth inhibitory effect against the LNCaP and C4-2B prostate Cancer lines, respectively.

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