Creation of bioactive non-natural flavonoids via combinatorial prenylation–glycosylation cascadesOA
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 nonnatural 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.
Hongjiao Zhang;Anxin Zhang;Jiatong Ji;Wen-Bing Yin
State Key Laboratory of Microbial Diversity and Innovative Utilization,Institute of Microbiology,Chinese Academy of Sciences,Beijing,ChinaState Key Laboratory of Microbial Diversity and Innovative Utilization,Institute of Microbiology,Chinese Academy of Sciences,Beijing,China Medical School,University of Chinese Academy of Sciences,Beijing,ChinaState Key Laboratory of Microbial Diversity and Innovative Utilization,Institute of Microbiology,Chinese Academy of Sciences,Beijing,China Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,ChinaState Key Laboratory of Microbial Diversity and Innovative Utilization,Institute of Microbiology,Chinese Academy of Sciences,Beijing,China Medical School,University of Chinese Academy of Sciences,Beijing,China Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei,China
化学化工
plant extractionmicrobial synthesisglycosylation cascadesenzymatic cascade catalysisantifungal propertiesthiscompoundbioactive compoundsnon natural flavonoids
《mLife》 2026 (2)
P.254-258,5
supported by the National Natural Science Foundation of China(grant number 32400062)the China Postdoctoral Science Foundation(grant number 2024M753451).
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