Identification of novel endophenaside antibiotics produced by Kitasatospora sp. MBT66

Abstract

Actinomycetes are a major source of bioactive secondary metabolites and are a focal point in the search for novel antimicrobial compounds that are needed to combat multidrug-resistant pathogens. Here, we report the discovery of several novel phenazine-type antibiotics produced by Kitasatospora sp. MBT66. These include the novel glycosylated endophenazines A-E (1-5), together with N-prenylated endophenazine F1 (6). Compounds 1 and 3 contain a 2'-O-methylation of the sugar moiety, which is rare in nature and reported for the first time in connection with phenazines. The structures of the new compounds were determined on the basis of their spectral data, including 1D and 2D NMR, HR-MS and the gene cluster responsible for the biosynthesis of phenazines was identified. All phenazine derivatives showed antimicrobial activity against the Gram-positive Bacillus subtilis, while compounds 1-3 and 5 also inhibited growth of the Gram-negative Escherichia coli.

Genus Kitasatospora, taxonomic features and diversity of secondary metabolites

“…The producing strain, compound name, activities of the compounds, reported by year, are shown in Table 3. 1,10,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] Setamycin possesses antitrichomonal and antifungal activities. Phosalacine possesses herbicidal activity.…”

Alkaliphilic Actinomycetes I.Isolation, Identification and Some Characterization

“…By studying all known species of this genus such as K. cystarginea (Kusakabe and Isono, 1988); K. cochleata and K. paracochleata (Nakagaito et al, 1992;Zhang et al, 1997); Kitasatospora kimorexae 90- GT-302 (yeo et al, 1994) K. cheerisanensis (Chung et al, 1999); K. cineracea and K. Niigatensis (Tajima et al, 2001) and Kitasatospora sp. MBT66 (Wu et al, 2015) and Takahashi (2017) confirmed that the four isolates differ in many physiological and phenotypic properties. The most important characteristic of these species is that they grow on alkaline media better than their growth on neutral media and that their physiological properties appear better on alkaline media than in neutral media and therefore can be considered new species of the Kitasatospora.…”

Quorum Sensing Inhibitors against <i>Chromobacterium violaceum</i> CV026 Derived from an Actinomycete Metabolite Library

“…130, methyphenazine-1-carboxylate, was isolated as a metabolite from S. luteoreticuli in 1971. 23) Recently, No. 130 was reported as a metabolite produced by Pseudomonas chlororaphis and strains of the genus Kitasatospora; moreover, the antifungal and anti-Gram-positive-bacterial activities of No.…”