Autor: |
Mohamed MMM; Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 221, 2800 Kgs. Lyngby, Denmark., Abboud MM; Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 221, 2800 Kgs. Lyngby, Denmark., Maleckis M; Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 221, 2800 Kgs. Lyngby, Denmark.; The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Søltofts Plads, Building 220, 2800 Kgs. Lyngby, Denmark., Souza LDO; Sino-Danish Center for Education and Research, Denmark; Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen, Denmark.; Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen, Denmark., Moreira JMA; Department of Drug Design and Pharmacology, University of Copenhagen, 2100 Copenhagen, Denmark., Gotfredsen CH; Department of Chemistry, Technical University of Denmark, Kemitorvet, Building 207, 2800 Kgs. Lyngby, Denmark., Weber T; The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Søltofts Plads, Building 220, 2800 Kgs. Lyngby, Denmark., Ding L; Department of Biotechnology and Biomedicine, Technical University of Denmark, Søltofts Plads 221, 2800 Kgs. Lyngby, Denmark. |
Abstrakt: |
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. |