The living environment of fungi is very complex.
In nature, the coexistence of fungi and bacteria, plants, animals and even humans is common
The rich species diversity and the variability of the living environment have led to the evolution of fungi to develop a unique set of mechanisms to respond to the environment and communicate with the organisms in the environment
This communication and response to nature prompt fungi to produce novel, complex and diverse types of active secondary metabolites, which provide abundant resources for new drug discovery
However, how do fungi communicate with microorganisms in the environment, and what are the molecular and biochemical mechanisms?
Yin Wenbing's research group at the Institute of Microbiology, Chinese Academy of Sciences has been working on the gene regulation mechanism and function of fungal secondary metabolites
Recently, the research group screened out an endophytic fungus , Epicoccum dendrobii, in the interaction between the model fungus Aspergillus nidulans and other fungi , which caused global changes in the secondary metabolic profile of Aspergillus nidulans ( Figure 1 ) .
In their further study, they found that during co-cultivation, Dendrobium epicoccus could induce significant changes in fungal secondary metabolites of at least 4 genera (Figure 1 ), indicating that this bacterium as a donor has a universal mechanism to stimulate The recipient bacteria respond by regulating changes in secondary metabolism, resulting in the production of some new secondary metabolites (Figure 1 ) .
However, how is this response achieved? Taking the co-culture system of Aspergillus nidulans and Dendrobium as a model, Yin Wenbing's research group analyzed the mechanism of its response from the aspects of biology, chemistry and genetics
Transcriptomic and metabolomic analysis showed that 15.
4% of the genes in Aspergillus nidulans were significantly up-regulated, 19% were significantly down-regulated, the production of 22 secondary metabolites was significantly increased, and 8 new structures of polyketides were identified Aspernidines (Figure 1 )
Transcriptome data analysis combined with gene knockout and complementation experiments proved that the key regulatory element in A.
nidulans in response to stimuli is the allelic protein of the global regulator VeA - VeA1 protein (deletion of the first 36 amino acids of VeA) , And it is involved in regulation in coordination with LaeA and VelB in the Velvet complex (Fig.
2 ) .
Their further study found that the downstream transcription factor SclB is regulated by the VeA1 protein and is involved in the regulation and activation of multiple biosynthetic gene clusters such as Aspernidines, revealing a complex gene regulatory network (Fig.
2 ) .
At the same time, this regulatory network was also validated in Aspergillus fumigatus
The universal co-culture system induced by the donor bacterium Dendrobium E.
nidulans ( A and B ); the global transcriptome and metabolome changes induced by the co-culture of D.
nidulans and Aspergillus nidulans .
and D )
This study is the first to propose the metabolic regulation function of the partially functionally deficient VeA1 protein, revealing that the co-culture between fungi is mediated by VeA1 , through the LaeA-VeA1-VelB complex, and then through the complex response regulatory network of the downstream transcription factor SclB (Fig.
2 ), which provides a solid theoretical basis for the study of the regulation mechanism of fungi - fungi co-culture.
It is a preliminary exploration of the response and communication mechanism under the coexistence of fungi and multiple species in nature.
Development provides effective strategies
Figure 2 Schematic diagram of the regulatory mechanism of global changes in secondary metabolites under fungal - fungus co-culture conditions
The above research results were quickly published in the international journal Science Advances ( https:// ) in the form of a research article , entitled " Fungal-fungal cocultivation leads to widespread secondary metabolite " alteration requiring the partial loss-of-function VeA1 protein ” .
Wang Gang and Special Research Assistant Dr.
Ran Huomiao from the Yin Wenbing Research Group of the Institute of Microbiology, Chinese Academy of Sciences are the co-first authors, and Researcher Yin Wenbing is the corresponding author .
The research was funded by the National Key R&D Program, the National Natural Science Foundation of China, the Basic Frontier Scientific Research Program of the Chinese Academy of Sciences from 0 to 1 Original Innovation Project, the Strategic Biological Resource Program of the Chinese Academy of Sciences, and the Postdoctoral Science Foundation .