Diversity in Chemical Structures and Biological Properties of Plant Alkaloids

Abstract

Phytochemicals belonging to the group of alkaloids are signature specialized metabolites endowed with countless biological activities. Plants are armored with these naturally produced nitrogenous compounds to combat numerous challenging environmental stress conditions. Traditional and modern healthcare systems have harnessed the potential of these organic compounds for the treatment of many ailments. Various chemical entities (functional groups) attached to the central moiety are responsible for their diverse range of biological properties. The development of the characterization of these plant metabolites and the enzymes involved in their biosynthesis is of an utmost priority to deliver enhanced advantages in terms of biological properties and productivity. Further, the incorporation of whole/partial metabolic pathways in the heterologous system and/or the overexpression of biosynthetic steps in homologous systems have both become alternative and lucrative methods over chemical synthesis in recent times. Moreover, in-depth research on alkaloid biosynthetic pathways has revealed numerous chemical modifications that occur during alkaloidal conversions. These chemical reactions involve glycosylation, acylation, reduction, oxidation, and methylation steps, and they are usually responsible for conferring the biological activities possessed by alkaloids. In this review, we aim to discuss the alkaloidal group of plant specialized metabolites and their brief classification covering major categories. We also emphasize the diversity in the basic structures of plant alkaloids arising through enzymatically catalyzed structural modifications in certain plant species, as well as their emerging diverse biological activities. The role of alkaloids in plant defense and their mechanisms of action are also briefly discussed. Moreover, the commercial utilization of plant alkaloids in the marketplace displaying various applications has been enumerated.

Keywords: alkaloid; biological activity; classification; defense; enzyme; modification.

Figure 1

Examples of alkaloids biosynthesized from the common skeleton. Multiple alkaloids are biosynthesized from the common skeleton represented inside the blue circle in different plant species. (A) Benzylisoquinoline alkaloids in Sacred lotus; (B) Steroidal alkaloids and their glycosides in tomato, potato, and eggplant; (C) Terpene indole alkaloids in C. roseus. The common skeleton undergoes multiple enzymatic conversions (M = methylation, O = oxidation, R = reduction, G = glycosylation, A = acetylation, H = hydroxylation, and E = epoxidation) represented by multiple arrows to form a variety of alkaloids. Key enzymatic reactions that are reported have been mentioned beside the arrows. The chemical structures of alkaloids are drawn from “ChemSpider: the Free Chemical Database”.

Figure 2

Alkaloid diversity in the plant kingdom. Alkaloids are produced in various parts of plants (such as the leaves, roots, seeds, etc.). Alkaloids are transported to required tissues mainly in response to various stress signals perceived from the environment. In the biosynthesis of alkaloids, enzymes of different families (MT: methyl transferase; GT: uridine-diphosphate-glycosyl transferase; AT: acyl transferase; CYP: cytochrome P450-monooxygenase and -reductase; SDR: short-chain dehydrogenase/reductase) act on alkaloidal substrates to generate diverse alkaloids with certain chemical modifications in numerous plant species. These enzymes catalyze the modification of alkaloidal substrates represented as A, B, C, D, and E in the presence of donors. SAM-S-adenosyl methionine acts as methyl donor for MTs; UDP-Glucose (UDP-Glc), UDP-rhamnose (UDP-Rha), UDP-xylose (UDP-Xyl), UDP-galactose (UDP-Gal), and UDP-glucuronic acid (UDP-GlcUA) are sugar donors for UDP-GTs; acyl-CoA thioesters and 1-O-β-glucose esters are acyl donors for ATs; NAD(P)H acts as an electron donor for CYPs and SDRs. Plant image is retrieved from BioRender (BioRender.com) (accessed on 20 March 2021). The chemical structures of alkaloids are drawn from “ChemSpider: the Free Chemical Database”.

Figure 3

Examples of chemical reactions taking place in alkaloid biosynthesis in plants. Enzymes catalyzing various reactions are indicated in blue. Red dotted circles indicate the addition of functional entities at the respective positions. (A) Methylation reactions in the biosynthesis of alkaloids in genus Corydalis, SoOMT1: scoulerine 9-O-methyltransferase, CoOMT: columbamine O-methyltransferase; (B) Methylation reactions in the biosynthesis of alkaloids in Sacred lotus, NnOMT5: O-methyltransferase 5, CNMT: coclaurine N-methyltransferase; (C) Glycosylation reactions in the biosynthesis of steroidal glycoalkaloids in Solanum lycopersicum, SlGAME: glycoalkaloid metabolism; (D) Acetylation reaction in the biosynthesis of morphinan alkaloids, SalAT: salutaridinol 7-O-acetyltransferase; (E) Acetylation reaction in the biosynthesis of cocaine; (F) Oxidative para-para phenol coupling reaction in the biosynthesis of colchicine; (G) Hydroxylation reaction followed by epoxidation reaction in the biosynthesis of tropane alkaloids, H6H: hyoscyamine 6β-hydroxylase; (H) Reduction reactions catalyzed by two stereospecific reductases in the biosynthesis of tropane alkaloids, TR-I/II: tropinone reductase I/II; (I) Reduction reaction in the biosynthesis of morphinan alkaloids, COR: codeinone reductase. The chemical structures of alkaloids are drawn from “ChemSpider: the Free Chemical Database”.

Figure 4

The role of alkaloids in plant defense. Alkaloids produced in different plant tissues, such as leaves, roots, bark, and seeds, are transported to local tissues for fighting against various predators such as pests, fungi, bacteria, and insect larvae, providing plants with protection against these predators. Alkaloids also stop the growth of other plants in the vicinity (allelopathy). Individual images of plant and predators are retrieved from BioRender (BioRender.com) (accessed on 20 March 2021).

Figure 5

The mechanism of action of alkaloids. Alkaloids act as a chemical barrier that protects plants from predators, such as herbivorous insects and vertebrates; pathogenic bacteria and fungi; and parasitic plants. Various mechanisms employed by plants using alkaloids create harmful effects in predators and are depicted in the figure.