Green Biosynthesis of Bioactive Streptomyces Metabolites Using Edible Mushrooms: Implications for Glycemic Control...

Diabetes mellitus is characterized by chronic hyperglycemia and oxidative stress, frequently leading to hepatic dysfunction. Functional food-based strategies that offer glycemic regulation and organ protection are increasingly sought as safer alternatives to long-term pharmacotherapy. This study explored the green biosynthesis of Streptomyces secondary metabolites using edible mushrooms and evaluated their potential for glycemic control and hepatic protection in diabetic rats. A Streptomyces isolate was molecularly identified by 16S rRNA sequencing and cultivated using Pleurotus ostreatus extract as a biological mediator for metabolite biosynthesis. Phytochemical composition and antioxidant activity were assessed in vitro. Streptozotocin-induced diabetic rats were treated orally with biosynthesized metabolite extracts (200 and 400 mg/kg). Fasting blood glucose, liver function enzymes, hepatic oxidative stress markers, histopathology, and molecular docking against diabetes-related targets were evaluated. The biosynthesized extract contained high levels of total phenolics (68.42 ± 3.15 mg GAE/g) and flavonoids (41.76 ± 2.08 mg QE/g), with strong DPPH scavenging activity (~81%). High-dose treatment reduced fasting blood glucose from > 300 to 129.6 ± 11.8 mg/dL by Day 28. Serum ALT, AST, and ALP levels were significantly lowered compared to diabetic controls, while hepatic malondialdehyde decreased from 4.92 ± 0.41 to 2.18 ± 0.21 nmol/mg protein. Molecular docking revealed strong binding affinities against α-glucosidase (-10.9 kcal/mol) and oxidative stress-related proteins (-7.9 kcal/mol). Edible mushroom-mediated biosynthesis of Streptomyces metabolites produced a bioactive extract with significant glycemic regulatory, antioxidant, and hepatoprotective effects, supporting its potential application as a functional food or nutraceutical for metabolic health management.