The Genome of Medicinal Plant Macleaya cordata Provides New Insights into Benzylisoquinoline Alkaloids Metabolism

Abstract

The overuse of antibiotics in animal agriculture and medicine has caused a series of potential threats to public health. Macleaya cordata is a medicinal plant species from the Papaveraceae family, providing a safe resource for the manufacture of antimicrobial feed additive for livestock. The active constituents from M. cordata are known to include benzylisoquinoline alkaloids (BIAs) such as sanguinarine (SAN) and chelerythrine (CHE), but their metabolic pathways have yet to be studied in this non-model plant. The active biosynthesis of SAN and CHE in M. cordata was first examined and confirmed by feeding C-labeled tyrosine. To gain further insights, we de novo sequenced the whole genome of M. cordata, the first to be sequenced from the Papaveraceae family. The M. cordata genome covering 378 Mb encodes 22,328 predicted protein-coding genes with 43.5% being transposable elements. As a member of basal eudicot, M. cordata genome lacks the paleohexaploidy event that occurred in almost all eudicots. From the genomics data, a complete set of 16 metabolic genes for SAN and CHE biosynthesis was retrieved, and 14 of their biochemical activities were validated. These genomics and metabolic data show the conserved BIA metabolic pathways in M. cordata and provide the knowledge foundation for future productions of SAN and CHE by crop improvement or microbial pathway reconstruction.

Genome of Tripterygium wilfordii and identification of cytochrome P450 involved in triptolide biosynthesis

“…Indeed, there are still CYP families, defined as phylogenetic clades with <40% amino acid sequence identity between them 32 , whose function remains unknown, with no biochemical activity yet assigned to any member 32 . Recently, whole-genome sequencing provides a comprehensive genetic resource and has become a practical approach to not only elucidation of natural product biosynthetic pathways, but also insight into their evolution, as well as improvement of their production 33,34 . Nevertheless, this must be coupled to other information directed more specifically at the natural product of interest.…”

Systematic identification of compounds in Macleaya microcarpa by high‐performance liquid chromatography/quadrupole time‐of‐flight tandem mass spectrometry combined with mass spectral fragmentation behavior of Macleaya alkaloids

“…The analysis of sample solutions was performed using a 1290 HPLC system (Agilent Technologies, Palo Alto, CA, USA) combined with a diode‐array detector (DAD) and a 6530 electrospray ionization (ESI) QTOF mass spectrometer (Agilent Technologies), as described previously . The separation was achieved on a XAqua C18 column (2.1 mm × 150 mm, 5 μm) (ACCHROM, Dalian, China), at 30°C, with 0.1% FA aqueous solution ( v / v , solvent A) and 0.1% FA/ACN (v/v, solvent B) as the mobile phase at a flow rate of 0.3 mL/min.…”

General and specialized tyrosine metabolism pathways in plants

“…Dopamine is an important neurotransmitter in the brain, and in plants, it is a precursor of numerous specialized metabolites, including phenethylisoquinoline alkaloids (e.g., colchicine) (Polturak and Aharoni 2018;Ehrenworth and Peralta-Yahya 2017), emetine alkaloids (e.g., emetine) (Nomura and Kutchan 2010), benzylisoquinoline alkaloids (e.g., morphine) (Schlager and Drager 2016;Liu et al 2017), catecholamines (e.g., epinephrine), and phenylethylamines (e.g., mescaline) (Rinner and Waser 2016). Dopamine can be synthesized via 3-hydroxylation of tyramine or decarboxylation of L-DOPA, but enzymes responsible for the 3-hydroxylation of tyrosine or tyramine are still unclear in plants.…”