Present status of Catharanthus roseus monoterpenoid indole alkaloids engineering in homo- and hetero-logous systems

Sharma, Abhishek; Amin, Dhruti; Sankaranarayanan, A.; Arora, Rajesh; Mathur, Anmol

doi:10.1007/s10529-019-02757-4

Cited by 36 publications

(31 citation statements)

References 74 publications

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“…Biosynthesis of the pharmaceutically important terpenoid indole alkaloids (TIAs) in Madagascar periwinkle ( C . roseus ) involves a pathway of more than 35 enzymatic steps in different cellular and subcellular compartments (Sharma et al 2020 ). Saiman et al ( 2018 ) overexpressed the C. roseus geraniol synthase gene in either plastids or cytosol of a non-alkaloid producing C. roseus cell line.…”

Section: Plant Metabolic Engineeringmentioning

confidence: 99%

Production of bioactive plant secondary metabolites through in vitro technologies—status and outlook

Wawrosch

Zotchev

2021

Appl Microbiol Biotechnol

102

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Medicinal plants have been used by mankind since ancient times, and many bioactive plant secondary metabolites are applied nowadays both directly as drugs, and as raw materials for semi-synthetic modifications. However, the structural complexity often thwarts cost-efficient chemical synthesis, and the usually low content in the native plant necessitates the processing of large amounts of field-cultivated raw material. The biotechnological manufacturing of such compounds offers a number of advantages like predictable, stable, and year-round sustainable production, scalability, and easier extraction and purification. Plant cell and tissue culture represents one possible alternative to the extraction of phytochemicals from plant material. Although a broad commercialization of such processes has not yet occurred, ongoing research indicates that plant in vitro systems such as cell suspension cultures, organ cultures, and transgenic hairy roots hold a promising potential as sources for bioactive compounds. Progress in the areas of biosynthetic pathway elucidation and genetic manipulation has expanded the possibilities to utilize plant metabolic engineering and heterologous production in microorganisms. This review aims to summarize recent advances in the in vitro production of high-value plant secondary metabolites of medicinal importance.Key points• Bioactive plant secondary metabolites are important for current and future use in medicine• In vitro production is a sustainable alternative to extraction from plants or costly chemical synthesis• Current research addresses plant cell and tissue culture, metabolic engineering, and heterologous production Graphical abstract

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Section: Plant Metabolic Engineeringmentioning

confidence: 99%

Production of bioactive plant secondary metabolites through in vitro technologies—status and outlook

Wawrosch

Zotchev

2021

Appl Microbiol Biotechnol

102

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“…The monoterpenoid moiety of strictosidine then undergoes extensive modifications catalyzed by various enzymes to form diverse MIAs, which represent over 2500 known metabolites 2 . Most of our current understanding of MIA biosynthesis is restricted to the vinca alkaloid synthesis pathway elucidated in Catharanthus roseus [4][5][6][7][8][9] . Camptothecin, another strictosidinederived molecule and one of the most potent anticancer MIAs, is the precursor for the commercial synthesis of topotecan and irinotecan, and several other camptothecin derivatives are in clinical trials at different stages 10,11 .…”

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confidence: 99%

Chromosome-level genome assembly of Ophiorrhiza pumila reveals the evolution of camptothecin biosynthesis

et al. 2021

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Plant genomes remain highly fragmented and are often characterized by hundreds to thousands of assembly gaps. Here, we report chromosome-level reference and phased genome assembly of Ophiorrhiza pumila, a camptothecin-producing medicinal plant, through an ordered multi-scaffolding and experimental validation approach. With 21 assembly gaps and a contig N50 of 18.49 Mb, Ophiorrhiza genome is one of the most complete plant genomes assembled to date. We also report 273 nitrogen-containing metabolites, including diverse monoterpene indole alkaloids (MIAs). A comparative genomics approach identifies strictosidine biogenesis as the origin of MIA evolution. The emergence of strictosidine biosynthesis-catalyzing enzymes precede downstream enzymes’ evolution post γ whole-genome triplication, which occurred approximately 110 Mya in O. pumila, and before the whole-genome duplication in Camptotheca acuminata identified here. Combining comparative genome analysis, multi-omics analysis, and metabolic gene-cluster analysis, we propose a working model for MIA evolution, and a pangenome for MIA biosynthesis, which will help in establishing a sustainable supply of camptothecin.

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“…The regulation of the TIA biosynthetic pathway is highly complex and the subject of current research (Patra et al 2013 ; Thamm et al 2016 ). Biosynthetic genes and transcriptional regulators, either individually or in combination, have been used to engineer the TIA pathway (Sharma et al 2020 ; Schweizer et al 2018 ; Tang and Pan 2017 ; Zhao and Verpoorte 2007 ; Zárate and Verpoorte 2007 ; Hughes et al 2004 ; Hughes and Shanks 2002 ; Morgan and Shanks 2000 ; Rijhwani and Shanks 1998 ; Peebles et al 2009 ). As a protocol for regeneration of transgenic C. roseus plants is not well established, cell lines and hairy roots are extensively used in the majority of these studies.…”

Section: Introductionmentioning

confidence: 99%

Terpenoid indole alkaloid biosynthesis in Catharanthus roseus: effects and prospects of environmental factors in metabolic engineering

et al. 2021

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Plants synthesize a vast array of specialized metabolites that primarily contribute to their defense and survival under adverse conditions. Many of the specialized metabolites have therapeutic values as drugs. Biosynthesis of specialized metabolites is affected by environmental factors including light, temperature, drought, salinity, and nutrients, as well as pathogens and insects. These environmental factors trigger a myriad of changes in gene expression at the transcriptional and posttranscriptional levels. The dynamic changes in gene expression are mediated by several regulatory proteins that perceive and transduce the signals, leading to up- or down-regulation of the metabolic pathways. Exploring the environmental effects and related signal cascades is a strategy in metabolic engineering to produce valuable specialized metabolites. However, mechanistic studies on environmental factors affecting specialized metabolism are limited. The medicinal plant Catharanthus roseus (Madagascar periwinkle) is an important source of bioactive terpenoid indole alkaloids (TIAs), including the anticancer therapeutics vinblastine and vincristine. The emerging picture shows that various environmental factors significantly alter TIA accumulation by affecting the expression of regulatory and enzyme-encoding genes in the pathway. Compared to our understanding of the TIA pathway in response to the phytohormone jasmonate, the impacts of environmental factors on TIA biosynthesis are insufficiently studied and discussed. This review thus focuses on these aspects and discusses possible strategies for metabolic engineering of TIA biosynthesis. Purpose of work Catharanthus roseus is a rich source of bioactive terpenoid indole alkaloids (TIAs). The objective of this work is to present a comprehensive account of the influence of various biotic and abiotic factors on TIA biosynthesis and to discuss possible strategies to enhance TIA production through metabolic engineering.

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Present status of Catharanthus roseus monoterpenoid indole alkaloids engineering in homo- and hetero-logous systems

Cited by 36 publications

References 74 publications

Production of bioactive plant secondary metabolites through in vitro technologies—status and outlook

Production of bioactive plant secondary metabolites through in vitro technologies—status and outlook

Chromosome-level genome assembly of Ophiorrhiza pumila reveals the evolution of camptothecin biosynthesis

Terpenoid indole alkaloid biosynthesis in Catharanthus roseus: effects and prospects of environmental factors in metabolic engineering

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