Abstract
Lovastatin is a competitive inhibitor of the enzyme hydroxyl methylglutaryl coenzyme A reductase (HMGR) in cholesterol biosynthetic pathway and hence used in the treatment of hyperlipidemia. Our results revealed that Aspergillus terreus of soil origin produce copious amount of lovastatin than its counterpart that are endophytic in origin. Bioinformatics analysis of whole genome sequence of A. terreus (AH007774.1), a soil isolate revealed the presence of lovastatin gene cluster (AF141924.1 and AF141925.1), whereas, endophytic fungi including a species of A. terreus showed no homology with the lovastatin gene cluster. Molecular studies aimed at generating physical evidence were performed to analyze the expression of lovastatin biosynthetic genes lovE (regulatory gene) and lovF (transcriptional regulatory factor) in soil and endophytic fungi. The target PCR amplification of lovE (1512bp) and lovF (749bp) were successful in a strain of soil isolate, Aspergillus terreus (KM017693), whereas the same was not achieved in endophytic fungi. This is the first report on comparative analysis of complementary DNA sequence of a soil isolate and endophytic fungi, which further substantiate the absence of lovastatin production by endophytic fungi. The significance for the lack of lovastatin by endophytic fungi is also discussed.
Highlights
Lovastatin is a fungal secondary metabolite that competitively inhibits conversion of 3 hydroxy 3 methyl glutaryl coenzyme A (HMG CoA) to mevalonate in cholesterol biosynthesis
Lovastatin production which is regulated by lovE and lovF has been widely studied and gene transfer studies indicate a pivotal role of lovE in cross platform gene transfer [6]
We have previously demonstrated that endophytic fungi as poor producers of lovastatin since none of the 54 endophytic fungi isolated by us from medicinal plants produced any detectable level of lovastatin even after 10 days of incubation [9]
Summary
Lovastatin is a fungal secondary metabolite that competitively inhibits conversion of 3 hydroxy 3 methyl glutaryl coenzyme A (HMG CoA) to mevalonate in cholesterol biosynthesis. To the above mixture 4 μl of the isolated total RNA was added with variable volume of PCR grade water making up the volume to 20 μl, mixed well and briefly centrifuged to collect the reaction mixture at the bottom of the reaction tube. Comparative studies on lovastatin production by SmF and SSF have been reported at molecular level in soil fungi.
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