Microbial flavonoids from Rhodococcus sp. FY-5 as functional substitutes for Ginkgo biloba leaf flavonoids under salt–copper stress

Abstract

Microbial-derived flavonoids are emerging as sustainable alternatives to plant polyphenols due to their potent antioxidant activities, structural similarity to plant metabolites, and scalability via fermentation. This study investigated the stress-induced metabolic responses of Rhodococcus sp. FY-5 (an endophyte from Ginkgo biloba) and evaluated the functional attributes of flavonoid extracts obtained under three conditions: ERF (Endophytic Rhodococcus sp. FY-5 flavonoids), NSCF (NaCl sequential Cu²⁺ stress flavonoids), and NCCF (NaCl combined Cu²⁺ stress flavonoids). Targeted LC-MS/MS profiling revealed distinct, strategy-dependent biosynthetic outputs. Compared with ERF, NCCF exhibited a 45.8 % increase in total flavonoid yield and a 62.3 % higher flavonol content, including myricetin and quercetin. Several major flavonoids in NCCF, such as quercetin, kaempferol, and rutin, matched those abundant in Ginkgo biloba leaves, indicating a comparable compositional profile. NCCF also enhanced 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity by 38.7 %, and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical cation scavenging activity by 42.0 %, while reducing intracellular reactive oxygen species (ROS) levels by 35.2 %. Correspondingly, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) rose by 29.4 %, 33.1 %, and 31.8 %. Relative to NCCF, NSCF further increased SOD, CAT, and GSH-Px activities by 41.5 %, 36.4 %, and 28.7 %, although the ROS clearance capacity was comparatively lower under NSCF. These consistent trends across metabolite profiles, antioxidant activities, and enzymatic defenses indicate the robustness of the observed stress-induced metabolic reprogramming in Rhodococcus sp. FY-5, which was stably maintained throughout the experimental period. This provides a viable approach to tailor microbial flavonoid profiles with enhanced oxidative protection and antimicrobial potential for functional food and nutraceutical applications.