Aim:The aim of the present study was to screen soil and endophytic fungi for production of lovastatin. Methodology: Soil fungi were isolated by dilution plating technique and endophytic fungi from selected medicinal plants by using standard procedures. All isolates were tested for lovastatin production by Solid State Fermentation (SSF) using wheat bran as substrate. Results: The soil isolate, Aspergillus terreus NCBI (KM017963) showed positive for lovastatin (1.0 mg/G DWS) whereas none of the endophytic fungi tested showed positivefor lovastatin production.
Diaporthe ampelina was isolated as an endophytic fungus from the root of Commiphora wightii, a medicinal plant collected from Dhanvantri Vana, Bangalore University, Bangalore, India. The whole genome is 59 Mb, contains a total of 905 scaffolds, and has a G+C content of 51.74%. The genome sequence of D. ampelina shows a complete absence of lovastatin (an anticholesterol drug) gene cluster.
We report the complete genome of Aspergillus terreus (KM017963), a tropical soil isolate. The genome sequence is 29 Mb, with a G+C content of 51.12%. The genome sequence of A. terreus shows the presence of the complete gene cluster responsible for lovastatin (an anti-cholesterol drug) production in a single scaffold (1.16).
Lovastatin is a competitive inhibitor of the enzyme hydroxymethyl glutaryl coenzyme A reductase (HMGR) in cholesterol biosynthetic pathway and hence used in the treatment of hyperlipidemia. In a previous study, we report a tropical soil isolate, Aspergillus terreus (KM017963), which produces ample amount of lovastatin than its counterpart that are endophytic in origin. Bioinformatic analysis of whole genome sequence of A. terreus (AH007774.1), a soil isolate revealed the presence of gene cluster (AF141924.1 & AF141925.1) responsible for lovastatin production, whereas endophytic fungi including a strain of A. terreus showed no homology with the lovastatin gene cluster. The molecular study was also carried out targeting PCR amplification of the two important genes, lovE (a regulatory gene) and lovF (transcriptional regulatory factor) in genomic and c-DNA of soil and endophytic fungi. Expression of the two genes was successful in A. terreus (KM017963), whereas the same was not achieved in endophytic fungi. To further validate our above findings, in the present study, the whole genome sequencing of A. terreus and a selected endophytic fungus, Diaporthe ampelina (Phomopsis) was performed. Lovastatin gene cluster, when aligned on the consensus sequence of both genomes, the entire lovastatin gene cluster was detected in a single scaffold (1.16) of A.terreus genome. On the contrary, there was a complete absence of lovastatin gene cluster in the genome of D. ampelina (an endophyte). The probable reasons for the absence of lovastatin gene cluster in endophytic fungi are discussed.
Lovastatin, an anti-cholesterol drug, is a potent inhibitor of the enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMG CoA reductase) that catalyses conversion of HMG CoA to mevalonate involved in cholesterol biosynthesis. Lovastatin does not only find a role as anti-cholesterol agent but also plays a key role as an anti-inflammatory agent, cancer cell apoptosis, renal function restoration, treatment for bone disorders etc. Production of statins has been undertaken by Submerged Fermentation (SmF) and Solid State Fermentation (SSF) by using fungi. In view of the advantages of SSF over SmF, the focus has shifted to production by SSF in recent years. The use of various agro based wastes as substrates has been proven. With recent developments in molecular biology and genome studies it has been able to decode genetic aspects of lovastatin gene expression levels. This review gives an insight into works reported on lovastatin production by SSF, various substrates employed, mutation studies, optimisation parameters, molecular studies and medical application of lovastatin.
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