HMG-CoA Reductase Inhibitory Activity of Leaf-associated Fungi

Background@#Cholesterol is an important biomolecule for cells. However, because of certain lifestyle, the amount of cholesterol can increase beyond what our bodies can consume. Increased intake may result in the accumulation of cholesterol in the blood leading to atherosclerosis that can lead to congestive heart failure. With the use of statins, cholesterol levels are reduced therefore lowering the risk for this disease. It does so by inhibiting the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the first committed enzyme in cholesterol biosynthesis. In light of the increasing cases of hypercholesterolemia, there is a need to discover novel classes of HMG-CoA inhibitors. @*Objective@#The primary objective of this study was to screen extracts of leaf-associated fungi for their capacity to inhibit hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the first committed enzyme in cholesterol biosynthesis. @* Methods@#Eight (8) plants were sampled for the fungal epiphytes and endophytes on their leaves. The fungal isolates were identified by sequencing the internal transcribed region (ITS) of the 18S rDNA. All fungal isolates were cultured in 20 flasks containing 300 mL potato dextrose broth at 30°C for 14 days. The culture broths were then subjected to reduction in volume using a rotary evaporator. HMG-CoA reductase inhibition assay was carried out using the ethyl acetate extracts from the culture broths. Reagent grade pravastatin was used as the positive control. @* Results@#There were a total of sixty-six (66) fungal taxa that were tested for their capacity to inhibit the enzyme HMG-CoA reductase. Of the 50 that tested positive, there were 25 families represented and 5 isolates were of uncertain status taxonomically (incertae sedis). There were also nine classes that were represented and the class with the most number of isolates was Sordariomycetes. The highest percentage inhibition was observed in Pestalotiopsis lespedezae with 65.01 % inhibition. The other fungi with notable inhibitory activities were Colletotrichum cymbidiicola (64.16%) and Schizophyllum commune (57.85%). @*Conclusions@#This study may be the first report of production of HMG-CoA reductase inhibitors in the genus Colletotrichum and in the other leaf-associated fungal taxa that tested positive for HMG-CoA reductase inhibition. It is therefore very promising that a novel statin compound, or even a new class of substances with antihypercholesterolemic bioactivity may be discovered from these leaf-associated fungal isolates. The crude extracts of these fungi are prime candidates for downstream fractionation for the subsequent isolation and structure elucidation of the bioactive compound.

Secondary metabolites from Corynespora cassiicola J9, an endophytic fungus associated with Blumea balsamifera (L.) DC / 药学学报

Chemical investigation on the rice culture of Corynespora cassiicola J9, an endophyte inhabiting in Blumea balsamifera (L.) DC. resulted in isolation of eight compounds, including a new depsidone derivative, corynether C (1), and seven analogues, corynether B (2), corynetherlactone A (3), corynether A (4), diaryl ether (5), corynesidone C (6), corynesidone D (7), and corynesidone A (8). Their structures were deduced based on 1D and 2D NMR spectroscopy, and HR-ESI-MS data. All of the isolated compounds were evaluated for inhibitory activities against Lissorhoptrus oryzophilus Kuschel by the leaf spray assay. Unfortunately, none of them showed inhibitory effects.

Antibacterial activity from co-culture of a Papua New Guinea fungal endophyte with bacillus subtilis

Fungal endophytes are fungi that reside in tissues of healthy living plants offering chemical protection and promoting growth of host plants. The chemistry and biological properties of their secondary metabolites from monoaxenic cultures have been extensively studied, but co-culture techniques using endophytes remain largely unexplored. Co-culture of bacteria with endophytic fungi have shown to be effective, leading to the discovery of novel chemistry while simultaneously addressing the problem of rediscovery of known metabolites from the monoaxenic culture techniques. Forty microliters (40μL) of culture broth consisting of monoaxenic and co-cultures were placed in separate agar wells with 5μg ciprofloxacin as positive control. The co-culture broth from one unidentified endophytic fungus with B. subtilis showed a marked zone of inhibition measuring 24.7 ±0.6 mm in comparison to ≥21.0 mm as the sensitivity range for ciprofloxacin against Escherichia coli while its monoaxenic culture exhibited no inhibition, but furthermore showed moderate activity (16.7 ± 1.2 mm) against B. subtilis. The isolation and chemical characterization of the active component and the mechanism of B.subtilis induction is under investigation. It is hoped that this unique Papua New Guinea endophyte will provide broad-spectrum antibiotic to combat the growing global problem of drug resistant infections.