Affiliation:
1. Collaborative Innovation Center of Ecological Civilization, School of Chemistry and Chemical Engineering, Hainan University, Haikou 570228, China
2. School of Life and Health Sciences, Hainan University, Haikou 570228, China
Abstract
Co-cultivation is a powerful emerging tool for awakening biosynthetic gene clusters (BGCs) that remain transcriptionally silent under artificial culture conditions. It has recently been used increasingly extensively to study natural interactions and discover new bioactive metabolites. As a part of our project aiming at the discovery of structurally novel and biologically active natural products from mangrove endophytic fungi, an established co-culture of a strain of Phomopsis asparagi DHS-48 with another Phomopsis genus fungus DHS-11, both endophytes in mangrove Rhizophora mangle, proved to be very efficient to induce the production of new metabolites as well as to increase the yields of respective target metabolites. A detailed chemical investigation of the minor metabolites produced by the co-culture of these two titled fungal strains led to the isolation of six alkaloids (1–6), two sterols (7, 8), and six polyketides (9–14). In addition, all the compounds except 8 and 10, as well as three new metabolites phomopyrazine (1), phomosterol C (7), and phomopyrone E (9), were not present in discrete fungal cultures and only detected in the co-cultures. The structures were elucidated on the basis of spectroscopic analysis, and the absolute configurations were assumed by electronic circular dichroism (ECD) calculations. Subsequently, the cytotoxic, immunosuppressive, and acetylcholinesterase inhibitory properties of all the isolated metabolites were determined in vitro. Compound 8 exhibited moderate inhibitory activity against ConA-induced T and LPS-induced B murine splenic lymphocytes, with IC50 values of 35.75 ± 1.09 and 47.65 ± 1.21 µM, respectively.
Funder
National Natural Science Foundation of China
Key Research Program of Hainan Province
Collaborative Innovation Center Foundation of Hainan University
Guangdong Key Laboratory of Marine Materia Medica Open Fund
Reference30 articles.
1. Lin, W., Li, G., and Xu, J. (2023). Bio-Active Products from Mangrove Ecosystems. Mar. Drugs, 21.
2. Biomolecules Produced by Mangrove-Associated Microbes;Xu;Curr. Med. Chem.,2011
3. Bioactive Natural Products Derived from Mangrove-Associated Microbes;Xu;RSC Adv.,2015
4. Natural Products from True Mangrove Flora: Source, Chemistry and Bioactivities;Wu;Nat. Prod. Rep.,2008
5. Biodiversity and Biotechnological Potential of Microorganisms from Mangrove Ecosystems: A Review;Thatoi;Ann. Microbiol.,2013