PreQ₀ Base, an Unusual Metabolite with Anti-cancer Activity from Streptomyces qinglanensis 172205

Author(s):

Dongbo Xu, Min Ma, Yongfeng Liu, Ting Zhou, Kexin Wang, Zixin Deng and Kui Hong   Pages 285 - 290 ( 6 )

Abstract:

PreQ₀ base (7-cyano-7-deazaguanine, compound 1) is the biosynthetic precursor of queuosine-tRNA and important synthetic intermediate for bioactive compounds. It was obtained for the first time as a new natural product from a mangrove actinomycete Streptomyces qinglanensis 172205, during the course of searching for anti-cancer compounds from marine microbes. PreQ₀ base showed anti-HeLa (IC₅₀ = 62.0 μg/ml) and anti-HepG2 (IC₅₀ = 80.6 μg/ml) activities, higher cytotoxicity than the positive control, fluorouracil. Furthermore, it exhibited weak α -glucosidase inhibitory activity, but no obvious antimicrobial and Aβ_1-42 fibrillation inhibitory activities. In silico analysis of the genome of the strain 172205 revealed a putative biosynthetic gene cluster directing the biosynthesis of PreQ₀ base. The gene cluster only contained three Open Reading Frames (ORFs), queC, queD and queE. The absence of the key gene queF encoding 7-cyano-7-deazaguanine reductase catalyzing PreQ₀ base to PreQ₁ base suggested that the strain only has the capacity of accumulation of PreQ₀ base as a metabolite, consistent with our observation in chemical identification.

Keywords:

Anti-cancer, biosynthetic gene cluster, mangrove actinomycete, natural product, PreQ₀ base.

Affiliation:

, , , , , , School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.

Graphical Abstract:

Read Full-Text article