Nature sub-journal: Discovery of a new way for fungi to synthesize the flavonoid naringenin

Flavonoids are a class of polyphenolic compounds mainly produced 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, p-coumaric acid (p-CA) is used as a precursor, and p-coumaryl-CoA ligase (4CL) and type III polyketone synthase chalcone synthase (CHS).
catalyzes the production of naringenin chalcone, followed by spontaneous isomerization of chalcone isomerase or pH change to produce naringenin
.
The production of flavonoids has been reported in fungi, but their synthesis and pathways have rarely been reported
.

Recently, Yin Wenbing's research group at the Institute of Microbiology, Chinese Academy of Sciences used a targeted genome mining strategy to discover a flavonoid naringenin synthase
from 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 heterozygosase, 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 results of FnsA KS domain phylogenetic analysis show 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 naringenin synthesis, the authors used an enzyme FnsA to synthesize naringenin in Saccharomyces cerevisiae, and on this basis, 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.
The successful de novo synthesis of the flavonoids isorhamine and acacia by engineering fnsA provides a new strategy
for the efficient production of flavonoids by microorganisms.

The relevant research results were published in the international authoritative journal Nature Communications on October 26, 2022, entitled "A fungal NRPS-PKS enzyme catalyses the formation of the flavonoid naringenin"
.
Zhang Hongjiao, a doctoral student of Yin Wenbing Research Group of the Institute of Microbiology of the Chinese Academy of Sciences, and Li Zixin, a graduate, are the co-first authors, and researcher Yin Wenbing is the corresponding author
.
The research was supported
by the National Key Research and Development Program of China, the National Natural Science Foundation of China, the International Cooperation Program of 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 Postdoctoral Science Foundation.

In recent years, Yin Wenbing's research group has published a series of papers in international journals such as Nat Commun, Sci Adv, JACS, Chem Sci, Acta Pharm Sin B, PloS Pathog and Nat Prod Rep to reveal the molecular mechanism, biosynthetic pathway and gene regulation mechanism of eukaryotic microbial secondary metabolites, providing new technologies and strategies for the discovery of new active compounds
。