Effects of Co-Cultivation on the Phenolic Composition and Bioactive Properties of Basidiomycete Mycelia: Antioxidant, Photoprotective, Anti-Tyrosinase, and In Silico Evidence

Basidiomycetes produce a wide range of bioactive metabolites, yet the effects of fungal co-cultivation on phenolic composition and associated biological properties remain poorly understood. This study investigated the phenolic composition and antioxidant, photoprotective, and anti-tyrosinase activities of mycelial extracts obtained from four basidiomycetes cultivated either alone or in paired cultures. Phenolic compounds were characterized by HPLC, and the identified metabolites were further evaluated using target prediction, enrichment analyses, PASS prediction, ADME profiling, and toxicity assessment. Nine phenolic compounds were identified across ten cultivation systems. Catechin and syringic acid were detected only in selected paired cultures, indicating that fungal interactions altered phenolic composition. The highest antioxidant activities were observed for P. sanguineus and T. polyzona cultivated alone, while SPF reached 39 in P. ostreatus, T. polyzona, Lentinus + Pycnoporus, and Pycnoporus + Trametes. Tyrosinase inhibition reached 92.7% in the axenic culture of P. ostreatus and remained above 90% in selected co-cultures. Computational analyses identified enrichment of biological processes related to oxidative stress and UV responses, as well as pathways including PI3K-Akt, FoxO, HIF-1, and p53. PASS prediction indicated that catechin, quercetin, and myricetin showed the highest probabilities for antioxidant activity, inhibition of lipid peroxidation and NADPH oxidase, and melanin synthesis inhibition, while ADMET predicted good solubility and high gastrointestinal absorption for most of the identified metabolites. Fungal interactions altered the phenolic composition of basidiomycete mycelia and influenced their biological activities, indicating that co-cultivation may be a useful strategy for modulating the production of bioactive metabolites.