Lovastatin Production by Endophytic Fungi Inhabiting Medicinal Plants and Evaluation of its Anticancer Property

Abstract

The current study aims to bioprospect endophytic fungi inhabiting medicinal plants for the newlineisolation and screening of potent lovastatin producers and scale up its production. It also newlinedemonstrates anticancer property of lovastatin against human ovarian teratocarcinoma cell line newlinePA1. From surface sterilized plant tissues of ten medicinal plants, 98 endophytic fungi were newlineisolated and screened for lovastatin production through submerged fermentation. Three isolates newline(designated as HL1, HL4 and HL5) from Hibiscus rosa-sinensis leaves were found to yield newlineconsistent amount of lovastatin across all levels of screening. The identification of the three newlineisolates was carried out by partial sequencing of 18S rRNA gene. HL1 was identified to be newlineMeyerozyma guilliermondii (GenBank Acc. No. KY780195); HL4 and HL5 as Aspergillus newlineterreus (GenBank Acc. No. KY780196 and KY780197, respectively). HL1 and HL5 isolates newlinewere subjected to solid state fermentation and various parameters involved in the fermentative newlineproduction of lovastatin were optimized through one-factor-at-a-time and statistical approaches. newlineVarious food and agrowastes were tested for their potency to serve as substrates and it was found newlinethat oil cakes supported maximum lovastatin production from both the isolates as compared to newlinewheat bran. An overall increase in lovastatin yield from M. guilliermondii and A. terreus through newlineprocess optimization was 37.5-fold and 42-fold respectively as compared to unoptimized newlineconditions. Strain improvement through genome shuffling resulted in 2.518-fold and 3.32-fold newlineincrease in lovastatin yield from M. guilliermondii and A. terreus, respectively as compared to newlinetheir wild types. The anticancer potential of lovastatin against PA1 cell line was investigated. newlineThe viability of the cells greatly decreased to 45.17% when treated with lovastatin at a newlineconcentration of 320 and#956;g/mL for 24 h. The drug was found to cause apoptosis through DNA newlinefragmentation. This is the first report on lovastatin production from the novel producer, M. newlineguilliermondii which produces lovastatin on par with the common producer A. terreus. This newlinestudy prompts to tap the potential of endophytic fungi to produce industrially significant newlinesecondary metabolites. Also, the clinical applicability of lovastatin in the treatment of ovarian newlinecancer can further be exploited through in vivo studies. newline