Research progress on the mechanisms of bidirectional fermentation-driven structural diversification of natural products

Natural medicines play a significant role in disease prevention and treatment due to their diverse biological activities. However, their complex chemical composition, low concentrations of active compounds, and toxicity limit their clinical application. Traditional processing and extraction methods suffer from low efficiency, resource wastage, and inadequate utilisation of active ingredients. Recently, bidirectional fermentation has gained attention for its unique advantage of 'reducing toxicity while enhancing efficacy'. By using natural medicines as a matrix and leveraging the metabolic activity of medicinal fungi, this technology improves the dissolution and biotransformation of active ingredients, generates new bioactive compounds, and simultaneously achieves the dual goals of enhanced efficacy and reduced toxicity. This paper reviews research progress on bidirectional fermentation in enhancing the utilisation of natural drug components, optimising pharmacological effects, and expanding application fields. It also explores its potential applications in biomanufacturing, functional foods, and modern health products.