Specific hydroxylation and glucuronidation of 2'-hydroxyflavanone by Streptomyces coeruleorubidus NRRL B-2569.

Abstract

Flavonoids constitute a class of natural compounds with varied bioactivities. Nevertheless, the potential health benefits of flavonoids for humans are often compromised by their low water solubility and limited bioavailability. In this study, four derivatives, namely 2',5'-dihydroxyflavanone (2), 5'-dihydroxyflavone-2'-O-β-d-glucuronide (3), and two isomers of hydroxyflavanone-2'-O-β-d-glucuronide (4 and 5), were biosynthesized from substrate 2'-hydroxyflavanone (1) through the specific hydroxylation and glucuronidation using Streptomyces coeruleorubidus NRRL B-2569. Product 2 was identified as a known compound while products 3-5 were structurally characterized as new structures through extensive 1D and 2D NMR analysis. The water solubility of obtained products 3-5 were enhanced by 36-340 times compared to the substrate. Moreover, the antioxidant assay revealed that product 3 exhibited improved 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity compared to the substrate, decreasing the logIC₅₀ from 10.77 ± 0.05 μM to 9.55 ± 0.05 μM. Compound 3 also displayed significantly higher anticancer activity than the substrate 2'-hydroxyflavanone against Glioblastoma 33 cancer stem cells (GSC33), decreasing the IC₅₀ from 25.05 μM to 7.07 μM. Thus, S. coeruleorubidus NRRL B-2569 stands out as an effective tool for modifying flavonoids, thereby enhancing their water solubility and bioactivities.