A new way for fungi to synthesize the flavonoid naringenin has been found

Flavonoids are a class of polyphenolic compounds produced mainly by plants and are widely
used in industry, food and pharmaceutical industries.
As a platform compound, naringenin is a key step in
the synthesis of flavonoids.
In plants and bacteria, with p-coumaric acid (p-CA) as a precursor, the formation of naringenin chalcone is catalyzed by p-coumarin coA ligase (4CL) and type III polyketone synthase chalcone synthase (CHS), and then spontaneous isomerization is catalyzed by chalcone isomerase or pH change to generate naringenin
.
Flavonoid production has been reported in fungi, but their synthetase and pathways have rarely been reported
.

Recently, the Yin Wenbing research group of the Institute of Microbiology of the Chinese Academy of Sciences used a targeted genome mining strategy to discover a flavonoid naringenin synthase
in plant endophytic fungi that is different from the conventional pathway.
The enzyme has a unique domain composition (A-T-KS-AT-DH-KR-ACP-TE) and is an NPRS-PKS heterozygosse identified as FnsA
.
Through heterologous expression, substrate feeding experiments and in vitro enzymatic reactions, it was confirmed that FnsA directly catalyzes 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 showed that FnsAPKS belongs to type I PKS, which is different from the traditional type III PKS (CHS).

In view of the novelty of FnsA catalyzing the synthesis of naringenin, researchers used an enzyme of fnsA to synthesize naringenin in Saccharomyces cerevisiae, and based on this, the biosynthetic pathway
of the plant flavonoids isorhamain and acacia was constructed from scratch.
The study confirmed that FnsA is a novel fungal naringenin synthase, and unlike the traditional naringenin synthesis pathway, FnsA can catalyze the direct synthesis of naringenin
from coumaric acid or p-hydroxybenzoic acid.
This study synthesizes the flavonoids isorhamine and acacia from scratch by engineering fnsA, providing a new strategy
for microorganisms to efficiently produce flavonoids.

The research is titled A fungal NRPS-PKS enzyme catalyses the formation of the flavonoid naringenin and published in Nature Communications
.
The research work is supported
by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the "0 to 1" original innovation project of the Basic Frontier Scientific 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 group has long been committed to the research of the mechanism and synthesis regulation mechanism of secondary metabolites, revealing the molecular mechanism, biosynthetic pathway and gene regulation mechanism of eukaryotic microbial secondary metabolites, and providing new technologies and strategies
for the discovery of new active compounds.

Source: Institute of Microbiology, Chinese Academy of Sciences

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