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Journal ArticleDOI

Biotechnological Approaches for Production of Anti-Cancerous Compounds Resveratrol, Podophyllotoxin and Zerumbone.

01 Jan 2017-Current Medicinal Chemistry (Curr Med Chem)-Vol. 25, Iss: 36, pp 4693-4717

TL;DR: This review focuses on the recent developments in the field of secondary metabolites from numerous plant sources, highlighting the use of micropropagation, cell suspension cultures, callus cultures, hairy root cultures, recombinant microbes and genetically modified higher plants.
Abstract: Secondary metabolites from numerous plant sources have been developed as anti- cancer reagents and compounds such as resveratrol, podophyllotoxin and zerumbone are of particular importance in this regard. Since their de novo chemical synthesis is both arduous and commercially expensive, there has been an impetus to develop viable, biotechnological methods of production. Accordingly, this review focuses on the recent developments in the field, highlighting the use of micropropagation, cell suspension cultures, callus cultures, hairy root cultures, recombinant microbes and genetically modified higher plants. Optimization of media and culture conditions, precursor feeding, immobilization and the use of chemical or physical elicitation in various protocols has led to an increase in resveratrol and podophyllotoxin production. Heterologous gene transformation of higher plants with stilbene synthase derived from Arachis hypogaea or Vitis vinifera lead to resveratrol production with the concomitant increase in resistance to plant pathogens. Interestingly, genetic transformation of Podophyllum hexandrum and Linum flavum with Agrobacterium rhizogenes resulted in Ri-T-DNA gene(s)-mediated enhancement of podophyllotoxin production. Zerumbone yields from tissue cultured plantlets or from suspension cultures are generally low and these methods require further optimization. In microbes lacking the native resveratrol or zerumbone biosynthesis pathway, metabolic engineering required not only the introduction of several genes of the pathway, but also precursor feeding and optimization of gene expression to increase their production. Data pertaining to safety and toxicity testing are needed prior to use of these sources of anti-cancer compounds in therapy.
Topics: Hairy root culture (53%), Resveratrol (52%)
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Journal ArticleDOI
Thomas Efferth1Institutions (1)
18 Mar 2019-Engineering
TL;DR: This review provides a timely overview of the advancements that have been made with callus cultures in these scientific fields and calls for more callus culture-based products to be developed and market.
Abstract: In ethnopharmacology, and especially in traditional Chinese medicine, medicinal plants have been used for thousands of years. Similarly, agricultural plants have been used throughout the history of mankind. The recent development of the genetic engineering of plants to produce plants with desirable features adds a new and growing dimension to humanity’s usage of plants. The biotechnology of plants has come of age and a plethora of bioengineering applications in this context have been delineated during the past few decades. Callus cultures and suspension cell cultures offer a wide range of usages in pharmacology and pharmacy (including Chinese medicine), as well as in agriculture and horticulture. This review provides a timely overview of the advancements that have been made with callus cultures in these scientific fields. Genetically modified callus cultures by gene technological techniques can be used for the synthesis of bioactive secondary metabolites and for the generation of plants with improved resistance against salt, draft, diseases, and pests. Although the full potential of callus plant culture technology has not yet been exploited, the time has come to develop and market more callus culture-based products.

81 citations


Journal ArticleDOI
Mihir Halder1, Sayantika Sarkar2, Sumita Jha2Institutions (2)
TL;DR: This is a comprehensive review about the progress in the elicitation approach to hairy root cultures from 2010 to 2019 and the information provided is valuable and will be of interest for scientists working in this area of plant biotechnology.
Abstract: Elicitation is a possible aid to overcome various difficulties associated with the large-scale production of most commercially important bioactive secondary metabolites from wild and cultivated plants, undifferentiated or differentiated cultures. Secondary metabolite accumulation in vitro or their efflux in culture medium has been elicited in the undifferentiated or differentiated tissue cultures of several plant species by the application of a low concentration of biotic and abiotic elicitors in the last three decades. Hairy root cultures are preferred for the application of elicitation due to their genetic and biosynthetic stability, high growth rate in growth regulator-free media, and production consistence in response to elicitor treatment. Elicitors act as signal, recognized by elicitor-specific receptors on the plant cell membrane and stimulate defense responses during elicitation resulting in increased synthesis and accumulation of secondary metabolites. Optimization of various parameters, such as elicitor type, concentration, duration of exposure, and treatment schedule is essential for the effectiveness of the elicitation strategies. Combined application of different elicitors, integration of precursor feeding, or replenishment of medium or in situ product recovery from the roots/liquid medium with the elicitor treatment have showed improved accumulation of secondary metabolites due to their synergistic effect. This is a comprehensive review about the progress in the elicitation approach to hairy root cultures from 2010 to 2019 and the information provided is valuable and will be of interest for scientists working in this area of plant biotechnology.

45 citations


Cites background from "Biotechnological Approaches for Pro..."

  • ...Furthermore, chemical synthesis is often not economically feasible because of their highly complex structures and stereospecificity [4,5]....

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Journal ArticleDOI
TL;DR: This review presents the combined efforts made during the past 15 years to engineer stilbene metabolic pathways in microbial cells, mainly the Saccharomyces cerevisiae baker yeast, the Escherichia coli and the Corynebacterium glutamicum bacteria.
Abstract: Numerous in vitro and in vivo studies on biological activities of phytostilbenes have brought to the fore the remarkable properties of these compounds and their derivatives, making them a top storyline in natural product research fields. However, getting stilbenes in sufficient amounts for routine biological activity studies and make them available for pharmaceutical and/or nutraceutical industry applications, is hampered by the difficulty to source them through synthetic chemistry-based pathways or extraction from the native plants. Hence, microbial cell cultures have rapidly became potent workhorse factories for stilbene production. In this review, we present the combined efforts made during the past 15 years to engineer stilbene metabolic pathways in microbial cells, mainly the Saccharomyces cerevisiae baker yeast, the Escherichia coli and the Corynebacterium glutamicum bacteria. Rationalized approaches to the heterologous expression of the partial or the entire stilbene biosynthetic routes are presented to allow the identification and/or bypassing of the major bottlenecks in the endogenous microbial cell metabolism as well as potential regulations of the genes involved in these metabolic pathways. The contributions of bioinformatics to synthetic biology are developed to highlight their tremendous help in predicting which target genes are likely to be up-regulated or deleted for controlling the dynamics of precursor flows in the tailored microbial cells. Further insight is given to the metabolic engineering of microbial cells with “decorating” enzymes, such as methyl and glycosyltransferases or hydroxylases, which can act sequentially on the stilbene core structure. Altogether, the cellular optimization of stilbene biosynthetic pathways integrating more and more complex constructs up to twelve genetic modifications has led to stilbene titers ranging from hundreds of milligrams to the gram-scale yields from various carbon sources. Through this review, the microbial production of stilbenes is analyzed, stressing both the engineering dynamic regulation of biosynthetic pathways and the endogenous control of stilbene precursors.

34 citations


Journal ArticleDOI
15 Jul 2019-Molecules
TL;DR: This review will mainly focus on the recent biotechnological advances for the production of resveratrol, including the various strategies used to produce its chemically diverse derivatives.
Abstract: The very well-known bioactive natural product, resveratrol (3,5,4′-trihydroxystilbene), is a highly studied secondary metabolite produced by several plants, particularly grapes, passion fruit, white tea, and berries. It is in high demand not only because of its wide range of biological activities against various kinds of cardiovascular and nerve-related diseases, but also as important ingredients in pharmaceuticals and nutritional supplements. Due to its very low content in plants, multi-step isolation and purification processes, and environmental and chemical hazards issues, resveratrol extraction from plants is difficult, time consuming, impracticable, and unsustainable. Therefore, microbial hosts, such as Escherichia coli, Saccharomyces cerevisiae, and Corynebacterium glutamicum, are commonly used as an alternative production source by improvising resveratrol biosynthetic genes in them. The biosynthesis genes are rewired applying combinatorial biosynthetic systems, including metabolic engineering and synthetic biology, while optimizing the various production processes. The native biosynthesis of resveratrol is not present in microbes, which are easy to manipulate genetically, so the use of microbial hosts is increasing these days. This review will mainly focus on the recent biotechnological advances for the production of resveratrol, including the various strategies used to produce its chemically diverse derivatives.

25 citations


Cites methods from "Biotechnological Approaches for Pro..."

  • ...Callus culture, plant culture, hairy root culture, cell suspensions culture, genetically modified transgenic plants, and recombinant microbes are well-established methods [65]....

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Journal ArticleDOI
TL;DR: All the aspects regarding phytostilbenes will be covered including their chemistry and biochemistry, regulation of their biosynthesis, biological activities in plants, molecular engineering of stilbene pathways in plants and microbes as well as their biotechnological production by plant cell systems.
Abstract: Covering: 1976 to 2020.Although constituting a limited chemical family, phytostilbenes represent an emblematic group of molecules among natural compounds. Ever since their discovery as antifungal compounds in plants and their ascribed role in human health and disease, phytostilbenes have never ceased to arouse interest for researchers, leading to a huge development of the literature in this field. Owing to this, the number of references to this class of compounds has reached the tens of thousands. The objective of this article is thus to offer an overview of the different aspects of these compounds through a large bibliography analysis of more than 500 articles. All the aspects regarding phytostilbenes will be covered including their chemistry and biochemistry, regulation of their biosynthesis, biological activities in plants, molecular engineering of stilbene pathways in plants and microbes as well as their biotechnological production by plant cell systems.

19 citations


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