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Research Discovers New Pathways for Fungi to Synthesize Flavonoids Naringin
Release time:
2021-11-12
Flavonoids are a class of polyphenolic compounds mainly produced by plants and widely used in industries such as industry, food, and pharmaceuticals. Naringin, as a platform compound, is a key step in the synthesis of flavonoids. In plants and bacteria, p-coumaric acid (p-CA) is used as the precursor to produce naringen chalcone catalyzed by p-coumaric coenzyme A ligase (4CL) and type III polyketone synthase chalcone synthase (CHS), and then the naringen isomerase catalyzes or changes the pH to produce naringen. The production of flavonoids has been reported in fungi, but there are few reports on their synthetases and pathways.
Flavonoids are a class of polyphenolic compounds mainly produced by plants and widely used in industries such as industry, food, and pharmaceuticals. Naringin, as a platform compound, is a key step in the synthesis of flavonoids. In plants and bacteria, p-coumaric acid (p-CA) is used as the precursor to produce naringen chalcone catalyzed by p-coumaric coenzyme A ligase (4CL) and type III polyketone synthase chalcone synthase (CHS), and then the naringen isomerase catalyzes or changes the pH to produce naringen. The production of flavonoids has been reported in fungi, but there are few reports on their synthetases and pathways.
Recently, the Yin Wenbing research group of the Institute of Microbiology, Chinese Academy of Sciences, using the strategy of targeted genome mining, found a flavonoid naringenin synthase in plant endophytic fungi that is different from the conventional pathway. This enzyme has a unique domain composition (A-T-KS-AT-DH-KR-ACP-TE) and is an NPRS-PKS hybrid enzyme identified as FnsA. Through heterologous expression, substrate feeding experiment and in vitro enzyme catalysis, it was confirmed that FnsA directly catalyzed the formation of naringenin with free aromatic acids (p-coumaric acid and p-hydroxybenzoic acid) as substrates. The phylogenetic analysis of the FnsA KS domain indicates that FnsAPKS belongs to type I PKS, which is different from the traditional type III PKS (CHS).
Given the novelty of FnsA catalyzing naringin synthesis, researchers utilized an enzyme of FnsA to synthesize naringin in brewing yeast, and based on this, constructed a biosynthetic pathway for plant flavonoids such as isorhamnetin and acacia from scratch. This study confirms that FnsA is a novel fungal naringin synthase, which is different from the traditional naringin synthesis pathway. FnsA can catalyze the direct synthesis of naringin from p-coumaric acid or p-hydroxybenzoic acid. This study provides a new strategy for efficient production of flavonoids by microorganisms through engineering fnsA De novo synthesis of plant flavonoids isorhamnetin and farnesin.
The relevant research results are titled A fungal NRPS-PKS enzyme catalysts of the formation of the flavonoid naringenin and published in Nature Communications. The research work has received support from the National Key R&D Program, the National Natural Science Foundation of China, the "From 0 to 1" original innovation project of the Basic Frontier Science Research Program of the Chinese Academy of Sciences, the Strategic Biological Resources Program of the Chinese Academy of Sciences, and the China Postdoctoral Science Foundation.
Yin Wenbing's research team has long been committed to studying the mechanism of secondary metabolites production and synthesis regulation mechanism, revealing the molecular mechanism, biosynthetic pathway, and gene regulation mechanism of secondary metabolites production in eukaryotic microorganisms, providing new technologies and strategies for the discovery of new active compounds.
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