Biotechnology is playing a vital alternative role in the production of pharmaceutical plant secondary metabolites to support industrial production and mitigate over-exploitation of natural sources. High-value pharmaceuticals that include alkaloids, flavonoids, terpenes, steroids, among others, are biosynthesized as a defensive strategy by plants in response to perturbations under natural environmental conditions. However, they can also be produced using plant cell, tissue, and organ culture techniques through the application of various in vitro approaches and strategies. In the past decades, efforts were on the clonal propagation, biomass and secondary metabolites production in the in vitro cultures of medicinally important plants that produce these molecules. In recent years, the effort has shifted towards optimizing culture conditions for their production through the application of cell line selection, elicitation, precursor feeding, two-phase co-culture among cell, tissue, and organ culture approaches. The efforts are made with the possibility to scale-up the production, meet pharmaceutical industry demand and conserve natural sources of the molecules. Applications of metabolic engineering and production from endophytes are also getting increasing attention but, the approaches are far from practical application in their industrial production.

Secondary metabolism of pharmaceuticals in the plant in vitro cultures: strategies, approaches, and limitations to achieving higher yield

Endophytes as in vitro production platforms of high value plant secondary metabolites.

Cancer is a major cause of death worldwide, with an increasing number of cases being reported annually. The elevated rate of mortality necessitates a global challenge to explore newer sources of anticancer drugs. Recent advancements in cancer treatment involve the discovery and development of new and improved chemotherapeutics derived from natural or synthetic sources. Natural sources offer the potential of finding new structural classes with unique bioactivities for cancer therapy. Endophytic fungi represent a rich source of bioactive metabolites that can be manipulated to produce desirable novel analogs for chemotherapy. This review offers a current and integrative account of clinically used anticancer drugs such as taxol, podophyllotoxin, camptothecin, and vinca alkaloids in terms of their mechanism of action, isolation from endophytic fungi and their characterization, yield obtained, and fungal strain improvement strategies. It also covers recent literature on endophytic fungal metabolites from terrestrial, mangrove, and marine sources as potential anticancer agents and emphasizes the findings for cytotoxic bioactive compounds tested against specific cancer cell lines.

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Endophytic Fungi-Alternative Sources of Cytotoxic Compounds: A Review.

Due to increasingly limited water resources, diminishing farmland acreage, and potentially negative effects of climate change, an urgent need exists to improve agricultural productivity to feed the ever-growing population. Plants interact with microorganisms at all trophic levels, adapting growth, developmental, and defense responses within a complicated network of community members. Endophytic fungi have been widely reported for their ability to aid in the defense of their host plants. Currently, many reports focus on the application of endophytic fungi with the capability to produce valuable bioactive molecules, while others focus on endophytic fungi as biocontrol agents. Plant responses upon endophytic fungi colonization are also good for the immune system of the plant. In this paper, the possible mechanisms between endophytic fungi and their hosts were reviewed. During long-term evolution, plants have acquired numerous beneficial strategies in response to endophytic fungi colonization. The interaction of endophytic fungi with plants modulates the relationship between plants and both biotic and abiotic stresses. It has previously been reported that this endophytic relationship confers additional defensive mechanisms on the modulation of the plant immune system, as the result of the manipulation of direct antimicrobial metabolites such as alkaloids to indirect phytohormones, jasmonic acid, or salicylic acid. Furthermore, plants have evolved to cope with combinations of stresses and experiments are required to address specific questions related to these multiple stresses. This review summarizes our current understanding of the intrinsic mechanism to better utilize these benefits for plant growth and disease resistance. It contributes new ideas to increase plant fitness and crop productivity.

Beneficial effects of endophytic fungi colonization on plants.

Endophytic fungi are abundant and have been reported from all tissues such as roots, stems, leaves, flowers, and fruits. In recent years, research into the beneficial use of endophytic fungi has increased worldwide. In this chapter, we critically review the production of a wide range of secondary metabolites, bioactive compounds from fungal endophytes that are a potential alternative source of secondary plant metabolites and natural producers of high-demand drugs. One of the major areas in endophytic research that holds both economic and environmental potential is bioremediation. During their life span, microbes adapt fast to environmental pollutants and remediate their surrounding microenvironment. In the last two decades, bioremediation has arisen as a suitable alternative for remediating large polluted sites. Endophytic fungi producing ligninolytic enzymes have possible biotechnological applications in lignocellulosic biorefineries. This chapter highlights the recent progress that has been made in screening endophytic fungi for the production and commercialization of certain biologically active compounds of fungal endophytic origin.

Aarthi Venugopalan

Papers

Endophytes as in vitro production platforms of high value plant secondary metabolites.

Enhanced camptothecin production by ethanol addition in the suspension culture of the endophyte, Fusarium solani

Effect of fermentation parameters, elicitors and precursors on camptothecin production from the endophyte Fusarium solani.