Endophytes: exploiting biodiversity for the improvement of natural product-based drug discovery

Abstract

Endophytes, microorganisms that colonize internal tissues of all plant species, create a huge biodiversity with yet unknown novel natural products, presumed to push forward the frontiers of drug discovery. Next to the clinically acknowledged antineoplastic agent, paclitaxel, endophyte research has yielded potential drug lead compounds with antibacterial, antiviral, antioxidant, insulin mimetic, anti-neurodegenerative and immunosuppressant properties. Furthermore, while being implicated in livestock neurotoxicosis, some endophyte-produced alkaloids have been shown to display insecticidal activity. The endophyte-host relationship is postulated to be a 'balanced antagonism'. Moreover, the plausibility of horizontal gene transfer (HGT) hypothesis is taken into account. Knowledge of the genetic background of endophytic natural product biosynthesis is discussed on the basis of loline alkaloids, ergopeptines, lolitrems and maytansinoids. The current dynamic progress in genomics will contribute to a better understanding of endophytic microbes and to further exploiting them as a source of pharmaceutically relevant compounds.

Screening the endophytic flora ofWollemia nobilisfor alternative paclitaxel sources

“…It is also noteworthy that the overwhelming majority of reports dealing with taxane-producing endophytes describe the fungal symbionts shortly after removal from their plant hosts, not taking full account of the possible impact and nature of the interdependencies between the naturally co-existing species (Staniek et al 2008;Hines and Zahn 2009). But one, very recent paper communicates an endeavour to reestablish the co-habitat by proposing a promising co-culture system for Taxus chinensis var.…”

“…Namely, if one accepts the notion that the origin for fungal paclitaxel production arose through lateral transfer of genetic information from Taxus spp., and accounts for the wide means of dispersal possessed by fungi, it is conceivable that fungal paclitaxel synthesizers may be found in many plants worldwide, including the relictual Wollemi pine. Furthermore, we hope to gain more insight into the fine-tuned equilibrium of plantmicrobe interactions (Staniek et al 2008;Hines and Zahn 2009) under evolutionary, environmental, physiological and genetic control. …”

Bioactive Polyesters in Marine and Plant Endophytic Fungi

“…The most widely accepted definition of an endophyte is given by Bacon et al; "microbes that colonize living, internal tissues of plants without causing any immediate, overt negative effects" [4]. The most frequently encountered endophytes are representatives of the fungi [5]. In the past few decades however, it has been realized that plants may contain countless, previously undetected, numbers of these microorganisms known as endophytes.…”

Metabolomics of Endophytic Fungi Producing Associated Plant Secondary Metabolites: Progress, Challenges and Opportunities

“…bacteria, and actinomycetes) have been discovered as endophytes. The most frequently encountered endophytes are fungi (Staniek et al, 2008). Fungal endophytes constitute an inexplicably diverse group of polyphyletic fungi ubiquitous in plants, and maintain an indiscernible dynamic relationship with their hosts for at least a part of their life cycle (Figure 2a,b).…”

“…On the one hand, the ecological aspects of endophytic fungi such as host range, evolutionary relatedness, infection, colonization, transmission patterns, tissue specificity, and mutualistic fitness benefits have been investigated relating to a plethora of plants (Arnold et al, 2003, 2007, Arnold, 2005, 2007Stone et al, 2004;Schulz &Boyle, 2005;Rodriguez et al, 2009) (Figure 2c). On the other hand, many discoveries have been made in isolating endophytic fungi, which have been shown to have the potential for de novo synthesis of various bioactive metabolites that may directly or indirectly be used as therapeutic agents against numerous ailments (Strobel and Daisy, 2003;Strobel et al, 2004;Zhang et al, 2006;Gunatilaka, 2006;Staniek et al, 2008;Suryanarayanana et al, 2009;Aly et al, 2010;Kharwar et al, 2011;Kusari & Spiteller, 2010. Rodriguez et al, 2009).…”