HMG-CoA Reductase Inhibitory Activity of Leaf-associated Fungi

Abstract

Background. Cholesterol is an important biomolecule for cells. However, because of certain lifestyle, theamount of cholesterol can increase beyond what our bodies can consume. Increased intake may result in theaccumulation 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 byinhibiting the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the first committed enzyme in cholesterolbiosynthesis. In light of the increasing cases of hypercholesterolemia, there is a need to discover novel classesof HMG-CoA inhibitors.
 Objective. The primary objective of this study was to screen extracts of leaf-associated fungi for their capacityto inhibit hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the first committed enzyme in cholesterolbiosynthesis.
 Methods. Eight (8) plants were sampled for the fungal epiphytes and endophytes on their leaves. The fungalisolates were identified by sequencing the internal transcribed region (ITS) of the 18S rDNA. All fungal isolates werecultured in 20 flasks containing 300 mL potato dextrose broth at 30°C for 14 days. The culture broths were thensubjected to reduction in volume using a rotary evaporator. HMG-CoA reductase inhibition assay was carried outusing 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 enzymeHMG-CoA reductase. Of the 50 that tested positive, there were 25 families represented and 5 isolates were ofuncertain status taxonomically (incertae sedis). There were also nine classes that were represented and the class withthe most number of isolates was Sordariomycetes. The highest percentage inhibition was observed in Pestalotiopsislespedezae 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 genusColletotrichum 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 extractsof these fungi are prime candidates for downstream fractionation for the subsequent isolation and structureelucidation of the bioactive compound.