Study on the secondary metabolites of the endophytic fungus Letendraea helminthicola A696 in spring sand kernels
Chinese medicine sand kernel belongs to the mature fruit of Zingiberaceae plants, widely distributed in southern China, Laos, Vietnam, Cambodia, and Thailand. Yangchun sand kernels produced in Yangchun City, Guangdong Province are the most famous. Spring sand kernels have the effects of moistening the stomach, regulating qi, and stabilizing pregnancy. Endophytic fungi that parasitize the roots of spring sand kernels have also become research objects for discovering novel structures and significant activities. Plant endophytic fungi are fungal species that inhabit plant tissues and coexist with plants. Plant endophytic fungi have rich species diversity and can produce secondary metabolites with novel and complex structures and diverse activities. Therefore, they have become important resources for discovering new natural active substances. The fungus Letendraea helminthicola is a scarce species, and research reports have shown that this genus of fungi related to sponges produces two compounds, 3-methyl-N – (2-phenylethyl) butanamide and cyclo (D-Pro-D-Phe), which have sewage control effects; Huang et al. reported the isolation of two new spirocyclic polyketide stereoisomers, letenketals A and B, containing a phenyldihydropyran ring and tetrahydrofuran ring skeleton, from the intestinal fungus Letendraea sp. in sea crabs. Antibacterial and anti-tumor activity tests showed almost no antibacterial activity, but weak anti-tumor activity at 40 μ M; Xu et al. isolated seven new polyketide compounds from the marine derived fungus Letendraea sp.5XNZ4-2, namely phomopsiketones D~G and letendronols A~C. Among them, phomopsiketone E showed weaker activity in inhibiting the production of nitric oxide in lipopolysaccharide activated macrophages. Our research group studied the chemical composition, anti-tumor and antibacterial activities of an endophytic fungus Letendraea helminthicola A696 isolated from spring sand kernels.

 

The fungus Letendraea helminthicola belongs to a rare microbial species. This article is the fourth report on the secondary metabolites of this genus of fungi. This genus of fungi produces diketopiperazines and spirocyclic polyketides. In this study, eight monomeric compounds were isolated from the fermentation broth of endophytic fungus A696 in spring sand kernels, enriching the types of secondary metabolites of this genus of fungi. Among them, compound 1 is a new sesquiterpene compound; Compound 2 is an antioxidant and the main raw material for synthesizing antioxidants such as 1076 and 1010; Compounds 3 and 4 are both compounds with an α – pyranone structure. Compound 3 has been reported as the first α – pyranone structure isolated from natural products and is usually synthesized from gibbepirone B; Compounds 5, 6, and 7 are all small molecule aromatic benzene ring compounds; Compound 8 is ergosterol, which has been applied in medicinal chemistry as a precursor of vitamin D2 and an intermediate in the production of hormone drugs. The crude extract of the bacterium showed certain antibacterial and anti-tumor activity, but compound 1 was found to have no antibacterial or anti-tumor activity through activity testing. It is likely that some secondary metabolites with antibacterial and anti-tumor activity were not successfully isolated from the crude extract. Therefore, large-scale fermentation can be carried out based on the amount of fermentation products to obtain active secondary metabolites; The liquid fermentation process lasted for up to 20 days, which may also be the reason for the production of some structurally simple basic metabolites in the culture medium, providing a lesson for future fermentation durations; On the other hand, studies have shown that sesquiterpenes have antibacterial, anticancer, insecticidal, and plant growth regulating activities. In the future, other activity tests can be conducted on this compound to explore its other biological activities.