A Review on the Composition and Biosynthesis of Alkaloids and on the Taxonomy, Domestication, and Cultivation of Medicinal Fritillaria Species

Abstract

Fritillaria is a perennial herb with medicinal properties. There are 158 Fritillaria species worldwide, 33 of which have reported therapeutic efficacy. Alkaloids are the principal constituents in Fritillaria. Fritillaria species growing at 2700–4000 m are the sources of extract namely Chuan Beimu (the Pharmacopoeia of the People’s Republic of China, 2020 Edition), with low biomass, mainly containing more 5α-cevanine isosteroidal alkaloids with cis-configuration. In contrast, species growing below 1500 m are usually taller than 50 cm, and they mainly contain more trans-configuration isosteroidal alkaloids. There are two schemes of the biosynthetic pathways of steroidal alkaloids with different frameworks and catalytic reactions and combined high-throughput omics data. Based on the distributed elevations, Fritillaria species were divided into three major categories, which met classification features based on phylogenetic analysis or morphological features. Artificial or in vitro cultivations are effective strategies for balancing economical requirements and ecological protection. Fritillaria species growing at lower altitudes can be cultivated by bulb reproduction, but species growing at higher altitudes still rely mainly on gathering a large number of wild resources. Integration of asexual tissue culture and bulb reproduction with sexual artificial or imitated wild cultivation may create a very promising and effective way to maintain sustainable industrial development of Fritillaria.

Alkaloids from Fritillaria przewalskii Bulbs and Their Anti‐Alzheimer's Disease Activities

“…The Fritillaria genus, membership of the Liliaceae family, is broadly spread in Asia, North America, and Europe, encompassing a total of 158 species. [6] Past chemical investigations to Fritillaria plants have unveiled lots of compounds, including isosteroidal, steroidal, and amide alkaloids, lignans, triterpenoids as well as diterpenoids. [7][8][9][10][11][12] Alkaloids are the principal constituents in Fritillaria.…”

“…[7][8][9][10][11][12] Alkaloids are the principal constituents in Fritillaria. [6] Fritillaria przewalskii Maxim. ex Batal., known colloquially as MinBei, widely growing in the provinces of Gansu, Sichuan, and Qinghai in China, and is one of the main sources of the medicinal herb "Chuan Beimu", included in the 2020 Edition of Pharmacopoeia of the People's Republic of China.…”

“…Past chemical investigations to Fritillaria plants have unveiled lots of compounds, including isosteroidal, steroidal, and amide alkaloids, lignans, triterpenoids as well as diterpenoids [7–12] . Alkaloids are the principal constituents in Fritillaria [6] . Fritillaria przewalskii Maxim.…”

Transcriptome Analysis of CYP450 Family Members in Fritillaria cirrhosa D. Don and Profiling of Key CYP450s Related to Isosteroidal Alkaloid Biosynthesis

“…A more promising approach for obtaining structurally complex natural products is the combination of genetic and metabolic engineering [11][12][13][14]. Because of the impact of the environment, Fritillaria is represented in China by various cultivars and variations, each of which has distinct qualities [15]. A multi-species metabolomics investigation revealed that F. cirrhosa contains abundant steroidal alkaloids, such as imperialine, suggesting that F. cirrhosa D. Don might be considered a suitable plant material for research on FISA biosynthesis [14].…”

“…ISA is then produced via initial cyclization of the central intermediate cycloartenol to cholesterol, followed by hydroxylation, oxidation, and transamination [14]. The majority of the research has been devoted to the cloning and control of functional genes upstream of the terpenoid biosynthesis pathway, including the 3-hydroxy-3-methylglutaryl coenzyme A reductase gene (HMGR), farnesyl diphosphate synthase (FPS), squalene synthase (SS), and cycloartenol synthase (CAS) [15]. Secondary metabolic pathways following cycloartenol generation are rarely studied, particularly the downstream CYP450 genes responsible for C-22, C-23, and C-26 hydroxylation in the steroidal alkaloid biosynthesis pathway.…”