The Integration of Metabolomics and Next-Generation Sequencing Data to Elucidate the Pathways of Natural Product Metabolism in Medicinal Plants.

Maria Benina,Youjun Zhang,Federico Scossa,Saleh Alseekh,Alisdair Fernie

doi:10.1055/a-0630-1899

Abstract

Plants have always been used as medicines since ancient times to treat diseases. The knowledge around the active components of herbal preparations has remained nevertheless fragmentary: the biosynthetic pathways of many secondary metabolites of pharmacological importance have been clarified only in a few species, while the chemodiversity present in many medicinal plants has remained largely unexplored. Despite the advancements of synthetic biology for production of medicinal compounds in heterologous hosts, the native plant species are often the most reliable and economic source for their production. It thus becomes fundamental to investigate the metabolic composition of medicinal plants to characterize their natural metabolic diversity and to define the biosynthetic routes in planta of important compounds to develop strategies to further increase their content. We present here a number of case studies for selected classes of secondary metabolites and we review their health benefits and the historical developments in their structural elucidation and characterization of biosynthetic genes. We cover the cases of benzoisoquinoline and monoterpenoid indole alkaloids, cannabinoids, caffeine, ginsenosides, withanolides, artemisinin, and taxol; we show how the "early" biochemical or the more recent integrative approaches-based on omics-analyses-have helped to elucidate their metabolic pathways and cellular compartmentation. We also summarize how the knowledge generated about their biosynthesis has been used to develop metabolic engineering strategies in heterologous and native hosts. We conclude that following the advent of novel, high-throughput and cost-effective analytical technologies, the secondary metabolism of medicinal plants can now be examined under the lens of systems biology.

Highlights

The first archeological evidences of the use of herbal remedies date back to prehistory: Neanderthals, for example, who have been long considered mainly meat-eaters, had instead already a good knowledge of the surrounding vegetation and adopted sophisticated diets: their dental plaques contained residues of several herbs, indicating the early consumption of plants, perhaps already for self-medication purposes [1].Written records of the use of medicinal plants–including recipes for preparing decocts and extracts–were common in Ancient Egypt, Greece, Rome, China, and in the Middle East.Scossa F et al The Integration of
We cover the cases of benzoisoquinoline and monoterpenoid indole alkaloids, cannabinoids, caffeine, ginsenosides, withanolides, artemisinin, and taxol; we show how the “early” biochemical or the more recent integrative approaches–based on omics-analyses–have helped to elucidate their metabolic pathways and cellular compartmentation
We summarize how the knowledge generated about their biosynthesis has been used to develop metabolic engineering strategies in heterologous and native hosts

Summary

Introduction

The first archeological evidences of the use of herbal remedies date back to prehistory: Neanderthals, for example, who have been long considered mainly meat-eaters, had instead already a good knowledge of the surrounding vegetation and adopted sophisticated diets: their dental plaques contained residues of several herbs, indicating the early consumption of plants, perhaps already for self-medication purposes [1].Written records of the use of medicinal plants–including recipes for preparing decocts and extracts–were common in Ancient Egypt, Greece, Rome, China, and in the Middle East.Scossa F et al The Integration of. In the second part of this review, we will summarize the knowledge acquired so far on the biosynthesis of specific compounds (ginsenosides, withanolides, artemisinin, and taxol) from other important medicinal plants where we believe integrative approaches could help further the elucidation of their secondary metabolism with a view on the discovery of novel metabolites of medicinal importance.

Results

Conclusion