Abstract
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 workCatharanthus 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.
Highlights
The medicinal plant Catharanthus roseus is the source of almost 200 terpenoid indole alkaloids (TIAs), including the anticancer therapeutics vinblastine and vincristine (De Luca et al 2014)
We have reported the critical roles of the CrMAPKK1-CrMAPK3/6 cascade in the regulation of TIA biosynthesis in C. roseus (Paul et al 2017)
The effects of environmental factors on regulatory genes have not been well studied, the expression of many key upstream pathway genes, such as TDC, STR, and G10H, are altered by environmental factors, such as drought, salt, low temperature, and UV, leading to change in TIA accumulation. These findings suggest that increasing upstream precursors using the key pathway genes or the transcription factors (TFs) regulating them will lead to increase of TIA accumulation
Summary
The medicinal plant Catharanthus roseus is the source of almost 200 terpenoid indole alkaloids (TIAs), including the anticancer therapeutics vinblastine and vincristine (De Luca et al 2014). The pharmaceutically important TIAs, vinblastine and vincristine, accumulate in extremely low quantities in C. roseus, leading to research efforts to enhance production through various strategies. Towards this end, the TIA biosynthetic pathway has been extensively studied, and the genes encoding key enzymes in the pathway have been identified and characterized (Fig. 1) (Miettinen et al 2014; Qu et al 2015, 2018, 2019; Stavrinides 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; Zarate and Verpoorte 2007; Hughes et al 2004; Hughes and Shanks 2002; Morgan and Shanks 2000; Rijhwani and Shanks 1998; Peebles et al 2009). We discuss whether the knowledge regarding the impacts of environmental factors on TIA pathway can be explored for metabolic engineering to increase TIA production
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