PreQ<sub>0</sub> Base, an Unusual Metabolite with Anti-cancer Activity from Streptomyces qinglanensis 172205

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