Microbial transformation of the sesquiterpene lactone tagitinin C by the fungus Aspergillus terreus

Abstract

The biotransformation of the sesquiterpene lactone tagitinin C by the fungus Aspergillus terreus MT 5.3 yielded a rare derivative that was elucidated by spectrometric methods. The fungus led to the formation of a different product through an unusual epoxidation reaction between C4 and C5, formation of a C3,C10 ether bridge, and a methoxylation of the C1 of tagitinin C. The chemical structure of the product, namely 1b-methoxy-3a-hydroxy-3,10b-4,5a-diepoxy-8b-isobutyroyloxygermacr-11(13)-en6a,12-olide, is the same as that of a derivative that was recently isolated from the flowers of a Brazilian population of Mexican sunflower (Tithonia diversifolia), which is the source of the substrate tagitinin C. The in vitro cytotoxic activity of the substrate and the biotransformed product were evaluated in HL-60 cells using an MTT assay, and both compounds were found to be cytotoxic. We show that soil fungi may be useful in the biotransformation of sesquiterpene lactones, thereby leading to unusual changes in their chemical structures that may preserve or alter their biological activities, and may also mimic plant biosynthetic pathways for production of secondary metabolites.

In vitro antimalarial studies of novel artemisinin biotransformed products and its derivatives

“…They can be used to modify chemical structures of biologically active products (Zhang et al, 2011), to prepare products which are difficult to obtain by conventional chemical methods (Adelin et al, 2012), to study the metabolism of xenobiotics (Abourashed et al, 1999) as well as to develop structure-activity relationship (SAR) models (Zhang et al, 2007). Till now, there are several reports on microbial transformations of sesquiterpene lactones (SLs) by fungi (Galal et al, 1999;Kumari et al, 2003;Lamare and Furstoss, 1990;Parshikov et al, 2006;Rocha et al, 2012). Some microorganisms are well known for their hydroxylation of artemisinin producing active metabolites .…”

The Remarkable Structural Diversity Achieved in ent-Kaurane Diterpenes by Fungal Biotransformations

“…For instance, a monoterpene commonly targeted is limonene, due to its wide availability from cheap sources such as waste from the orange juice industry and its great potential as a substrate for the production of fragrances [4]. Functionalized derivatives of sesquiterpenes [5,6] and triterpenes [7] have also been obtained as fungal metabolites. Reports on the biotransformation of many different types of diterpenes, such as labdane [8], trachylobane [9,10], stemodane [11], aphidicolane [12], pimaradiene [13], abietane [14], taxane [15], atisane [16], and beyerane [17] are also very frequently found in the literature.…”

Transformations of Some Sesquiterpene Lactones by Filamentous Fungi and Cytotoxic Evaluations

“…The main types of reported biotransformations of SLs with various filamentous fungi include hydrogenations, hydroxylations, acylations, methoxylations, and epoxidations, among others . Particularly, the biotransformations of the antimalarial sesquiterpene lactone artemisinin or related compounds have been studied …”