Progress in Biosynthesis of Natural Products of Higher Fungi in Kunming Plants

Due to the special growth mode and the important role in the ecological environment, higher fungi can produce novel compounds with novel structures and good biological activity. These natural products provide a leading resource for the development of drugs and biological pesticides, such as fungicides strobilurins. Conjugulators), antibiotics pleuromutilins (pleuromutilin), antitumor illudins (inhibitors), and omphalotins that inhibit nematodes. With the development of genome sequencing and bioinformatics technology, breakthroughs have been made in the research of biosynthesis of natural products. However, due to the complex genetic background and genetic manipulation difficulties, the biosynthesis of natural products of higher fungi has lagged behind bacteria and lower fungi (Front Microbiol. 2015, 6, 127).

Kunying Institute of Botany, Kunming Institute of Botany, Chinese Academy of Sciences The Zeng Ying Research Group of the State Key Laboratory for the Sustainable Utilization of Plant Resources in the West has cooperated with Liu Jikai's research team in recent years and is committed to the study of secondary metabolism of higher fungi and biosynthesis of natural products. Previous studies revealed that the novel pancreatic lipase inhibitor, vibralactone, was produced in Boreostereum vibrans, demonstrating that the rare 4/5 fusion bicyclic lactone skeleton of diphtheria was neither polyketide nor polyketide. Instead of a sesquiterpene source, it is derived from the aromatic ring of the shikimic acid pathway (Angewandte Chemie International Edition 2013, 52: 2298–2302). The wonderful biosynthetic pathway of diphtheria shows the extraordinary creativity of higher fungi.

Recently, doctoral student Yang Yanlong and other researchers have integrated the use of organic chemistry and biochemical and molecular biology techniques to further study the biosynthetic mechanism of structurally diverse mixed terpenoids in brown cap T. gonorrhoeae through precursor-directed biosynthesis. figure 1). For the first time, the monooxylase VibMO1 involved in the key reactions of oxidative decarboxylation was identified at the genetic and enzymatic levels (Fig. 2), thus confirming the long-term hypothesis that isoprenyl-substituted hydroquinones (sometimes called It is probably due to the oxidative decarboxylation of the isopentenyl-substituted p-hydroxybenzoic acid. The discovery of the monooxygenase VibMO1 also provided important clues for the identification of an enzyme gene that catalyzes a similar reaction during the formation of a coenzyme Q in eukaryotes. At the same time, the study also demonstrated the formation of a mixture of phletocins from isopentenyl-p-hydroxybenzyl alcohol through a divergent pathway (Figure 3), among which 3-substituted γ-butyrolactones. The novel biosynthetic pathway of the compound Vibralactone G (8) was reported for the first time in natural product chemistry. The results of the study deepen the understanding of the mechanism of structural diversity of secondary metabolites and open up new horizons for the study of biosynthesis of natural products. In addition, graduate students Zhou Hui et al. also identified a sesquiterpene synthase BvCS that catalyzes the formation of FPP as a major product of δ-cadinol (Figure 4). This enzyme is likely to be involved in brown caps. Biosynthesis of Borrevibrins from the phloem.

The above research results were published in Angewandte Chemie International Edition (2016, 55: 5463–5466) and Natural Products and Bioprospecting, respectively. The study was funded by the National Natural Science Foundation of China (21572237, 81561148013). The static configuration of compound 11a was determined by computational chemistry by Yang Jing, the analysis and test center of Kunming Institute of Plant Science.

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