P450s controlling metabolic bifurcations in plant terpene specialized metabolism

Abstract

Catalyzing stereo- and regio-specific oxidation of inert hydrocarbon backbones, and a range of more exotic reactions inherently difficult in formal chemical synthesis, cytochromes P450 (P450s) offer outstanding potential for biotechnological engineering. Plants and their dazzling diversity of specialized metabolites have emerged as rich repository for functional P450s with the advances of deep transcriptomics and genome wide discovery. P450s are of outstanding interest for understanding chemical diversification throughout evolution, for gaining mechanistic insights through the study of their structure–function relationship, and for exploitation in Synthetic Biology. In this review, we highlight recent developments and examples in the discovery of plant P450s involved in the biosynthesis of industrially relevant monoterpenoids, sesquiterpenoids, diterpenoids and triterpenoids, throughout 2016 and early 2017. Examples were selected to illustrate the spectrum of value from commodity chemicals, flavor and fragrance compounds to pharmacologically active terpenoids. We focus on a recently emerging theme, where P450s control metabolic bifurcations and chemical diversity of the final product profile, either within a pathway, or through neo-functionalization in related species. The implications may inform approaches for rational assembly of recombinant pathways, biotechnological production of high value terpenoids and generation of novel chemical entities.Graphical Abstract

The genome of the medicinal plant Andrographis paniculata provides insight into the biosynthesis of the bioactive diterpenoid neoandrographolide

“…This is similar to the number found in other angiosperms (Nelson and Werck‐Reichhart, ). Members of the CYP71 and CYP76 families have been shown to be involved in labdane‐related diterpenoid biosynthesis in other Lamiales species (Banerjee and Hamberger, ). Genes for a total of 43 CYP71 and 14 CYP76 family members were found in the A. paniculata genome (Table S14).…”

Phytochemical and comparative transcriptome analyses reveal different regulatory mechanisms in the terpenoid biosynthesis pathways between Matricaria recutita L. and Chamaemelum nobile L.

“…CYPs (cytochrome P450 enzymes) not only play indispensable roles in plant primary metabolism but are also important in secondary metabolism. Recent studies have shown that CYPs function as modification enzymes in terpenoid biosynthesis [48,49]. In addition, we identified many CYPs that interact with proteins involved in terpenoid biosynthesis in PPINs for German chamomile and Roman chamomile, and we found that there are more CYP-interacting proteins in German chamomile compared to Roman chamomile.…”

Strategies for the production of biochemicals in bioenergy crops

“…Menthol is used in flavor and fragrance products for its cooling and refreshing sensation. It has an increasing global demand of 30,000 MT/year [153] and a market value estimated at US $3.85 billion in 2018, which is expected to reach US $5.59 billion by the end of 2025 with a CAGR of 4.8% (2019-2025) [266,267].…”

“…The enantiomer 4S-limonene is abundant in peppermint, spearmint, and perilla [278], and its biosynthesis has been extensively studied [279]. Because of a fairly high boiling point (176 °C) and high standard enthalpy of combustion (− 6100 kJ/mol), limonene represents a promising highdensity isoprenoid-derived biofuel [267]. The biosynthesis of limonene requires two biosynthetic enzymes for the formation of GPP by GPPS and cyclization of GPP into limonene catalyzed by LMS [280].…”