Progress was made in the study of fungal secondary metabolite activation, biosynthesis and its regulatory mechanism.

Fungi, as the second largest living organism in nature, are an important source of natural drug creation.
, however, a large number of fungal genome sequencing shows that more than 90% of the secondary metabolite synthesis gene clusters in fungi are silent, greatly limiting the discovery of metabolites and their synthesis mechanisms.
The National Key Laboratory of Fungiology of the Institute of Microbiology of the Chinese Academy of Sciences, In response to the problem of the silence of a large number of gene clusters in fungi, the group has long been engaged in research from genes to secondary metabolites, mainly in the direction of fungal secondary metabolite activation, biosynthesis and its regulatory mechanism research, and in the past year has achieved the following systematic and original results: 1) using oscic genetic strategies to excavate the diversity of natural products of fungi Through the targeted genetic control factors in the plant endogenous fungus fig figs, the team found that the sub-metabolite fingerprint map of the bacteria had undergone great changes (Figure 1), from which 15 new polycodone natural products were isolated and identified, and the synthetic pathway of the product Ficiolide A was illustrated by isotope tracer.
in this study, the team greatly shortened the cycle of fungal transformation by improving the genetic transformation technology, which provided an efficient method for the discovery of new natural products.
the study was published in Organic Letters (2016, 18 (8), 1832-1835).
, an assistant researcher in the Wenbing Task Force, was the first author of the article, and Yu Wenbing was the author of the article communication.
the study was funded by the Chinese Academy of Sciences' "100-person program" and the National Natural Science Foundation.
2) To clarify the biosynthetic pathway of the important antibacterial paleoenvirus peptide antibiotic leucinostatins, the team predicted the synthetic gene cluster of the lipopypes antibiotic leucinostatins by sequencing the genome of the pale cyanostatins and combining it with comparative genomic analysis.
the synthetic gene clusters of leucinostatins by knocking out the genetics of the candidate genes, and analyzed their synthesis pathways (Figure 2).
this work has laid a theoretical foundation for the development of various pest and disease drugs for the control of plant worms.
findings were published in the international journal PloS Pathogens (12 (7): e1005685).
Wenbing and Xie Qiyan, researchers of the Chinese Academy of Agricultural Sciences, are the co-authors of the article, and Liu Zhiguo, Ph.D., Dr. Wang Gang of the Academy of Agricultural Sciences, and Lin Runmao are the first authors of the article.
3) Pioneering the application of fungal glycosyl transferase to natural product pharmacogenic improvement The use of glycosylation to modify active natural product modification is an effective means to modify its medicinal nature, currently often using fungi (nearly 40%) as the host for biological conversion to obtain, but so far has not been found from fungi working glycosyl transferase.
team used bio-transformation-oriented RNA-Seq technology to discover and identify the first glycosyl transferase from permafrost mold and successfully express the soluble protein.
study found that the enzyme has a wide range of substrate clutter and single-dimensional selectivity, mainly UDP-glucose as a sugar-based supply, can accept 73 phenolic substances-based pharmaceutical skeleton compounds as substrates, oxygen glycosylation reaction, the yield of the main product can reach more than 60%.
It is worth noting that the enzyme is uniquely proprietary to the catalytic activity of phenolic substrates containing isoprene-based, and that the location of glycosylation occurs mainly on hydroxyl groups of isoprene-based neighbors, indicating the complexity of the enzyme catalysis (Figure 3).
, a researcher at the Institute of Microbiology, carried out a computer simulation of the structure and explained the particularity of its catalysis.
the findings were published in the journal Applied Chemistry, Advanced Synthesis and Catalysis.
Yu Wenbing and Ye Min, a researcher at Peking University's School of Pharmacy, are the co-authors of the article, and Feng Jin and Zhang Peng of the Yi Wenbing Task Force are the first authors of the article, and the study has been funded by the Chinese Academy of Sciences' "100 People Program" special fund and the National Natural Science Foundation of China.
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