Title:PreQ<sub>0</sub> Base, an Unusual Metabolite with Anti-cancer Activity from Streptomyces qinglanensis 172205
VOLUME: 15 ISSUE: 3
Author(s):Dongbo Xu, Min Ma, Yongfeng Liu, Ting Zhou, Kexin Wang, Zixin Deng and Kui Hong
Affiliation:School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
Keywords:Anti-cancer, biosynthetic gene cluster, mangrove actinomycete, natural product, PreQ0 base.
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 Aβ1-42 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.
