Work

Creation of bioactive non‐natural flavonoids via combinatorial prenylation–glycosylation cascades

Year: 2026

Type: article

Abstract: Impact statement Flavonoids have significant medicinal potential; however, the reliance on plant extraction for their production poses a substantial barrier to their practical application. Innovative approaches like enzymatic cascade catalysis and microbial synthesis present promising avenues for the efficient production of these structurally complex compounds. In this study, two non‐natural flavonoids (compounds 7 and 8 ) were synthesized, with compound 7 displaying antifungal properties. This was achieved through the cascade enzymatic catalysis of naringenin, a key intermediate in flavonoid biosynthesis, using glycosyl‐ and prenyltransferases. Additionally, metabolic engineering was used to bolster the supply of the dimethylallyl pyrophosphate precursor via the isopentenol utilization pathway in Escherichia coli , facilitating the de novo creation of non‐natural flavonoids. Consequently, the titers of compounds 7 and 8 reached 47.4 and 6.6 mg/l, respectively. This research highlights the potential of modular enzyme assembly in generating bioactive flavonoid derivatives and establishes a sustainable platform for the discovery of non‐natural flavonoids.

Source: mLife

DOI: 10.1002/mlf2.70063

Authors: Hongjiao Zhang, Anxin Zhang, Jiatong Ji, Wen‐Bing Yin

Institutions: Chinese Academy of Sciences, Institute of Microbiology, University of Chinese Academy of Sciences, University of Science and Technology of China

Language: English

Topic: Biochemical and biochemical processes

Subfield: Biotechnology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: diamond

Funders: National Natural Science Foundation of China, China Postdoctoral Science Foundation

Awards: G2127225313, G5629145292