Abstract
Plant endophytic microorganisms represent a largely untapped resource for new bioactive natural products. Eight polyketide natural products were isolated from a mangrove endophytic fungus Phomosis sp. A818. The structural elucidation of these compounds revealed that they share a distinct feature in their chemical structures, an oxygen-bridged cyclooctadiene core skeleton. The study on their structure–activity relationship showed that the α,β-unsaturated δ-lactone moiety, as exemplified in compounds 1 and 2, was critical to the cytotoxic activity of these compounds. In addition, compound 4 might be a potential agonist of AMPK (5′-adenosine monophosphate-activated protein kinase).
Highlights
Mangrove endophytic fungi are a rich source of structurally novel and biologically diverse natural products that could be useful in the development of new pharmaceutical agents [1,2].During the course of our exploration for chemical constituents from the endophytic microorganisms of mangrove, we isolated a series of new compounds with various bioactivities [3,4,5,6,7,8]
We used the genome shuffling approach to generate high MED-producing strains, which were screened by the high-throughput screening method, ‘Antimicrobial-TLC-HPLC’ (ATH) [16,17]. These efforts led to several high yield strains for MED analogs, including strain A818, in which the yield increased over 200-fold
AMPK and acetyl-CoAcarboxylase carboxylase (ACC) phosphorylation in NIH/3T3 cells treated with compound 4 for indicated time. β-Actin β-Actin was used as a loading control; (D) Western blot analyses of AMPK and ACC phosphorylation was used as a loading control; (D) Western blot analyses of AMPK and ACC phosphorylation in 3T3-L1 in 3T3-L1 cells treated with compound 4 for 2 h. β-Actin was used as a loading control. (Pho-AMPK: cells treated with compound 4 for 2 h. β-Actin was used as a loading control. (Pho-AMPK: phosphorylated AMPK; Pho-ACC: phosphorylated ACC)
Summary
Mangrove endophytic fungi are a rich source of structurally novel and biologically diverse natural products that could be useful in the development of new pharmaceutical agents [1,2]. We used the genome shuffling approach to generate high MED-producing strains, which were screened by the high-throughput screening method, ‘Antimicrobial-TLC-HPLC’ (ATH) [16,17]. These efforts led to several high yield strains for MED analogs, including strain A818, in which the yield increased over 200-fold. We describe the isolation, structure elucidation, and bioactivity test of eight natural products of the MED class from strain A818, which was derived from the mangrove endophytic fungus Phomosis sp.
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