Biosynthesis of alkaloids in Amaryllidaceae plants: a review

Recent Progress in Amaryllidaceae Biotechnology

“…Recently, in attempts to respond to the demand of Amaryllidaceae alkaloids, substantial efforts have been made to improve the yields and biosynthesis efficiency of target molecules, including the application of metabolic engineering technologies. In contrast to the fast-growing knowledge about Amaryllidaceae alkaloids chemistry and pharmacological activities, very little is known about their biosynthesis, the responsible functional and regulatory genes, and the molecular mechanisms underlying its regulation [ 1 , 58 , 59 ]. Although rapid advances in omics technologies over the past few years have led to significant discoveries in Amaryllidaceae alkaloid biosynthesis, there are still many unknown details about their biosynthetic pathway ( Figure 2 ).…”

“…The biosynthesis of Amaryllidaceae alkaloids is a complex process and is a result of coordinated action of enzymes from different biosynthetic pathways of primary, secondary and specialized cell metabolism ( Figure 2 ). According to Desgagne’-Penix [ 59 ], the biosynthetic pathway of Amaryllidaceae alkaloids could be provisionally divided into five stages: (1) Biosynthesis of the two aromatic amino acid L-phenylalanine and L-tyrosine, which are the building blocks of Amaryllidaceae alkaloids; (2) Formation of 3,4-dihydroxybenzaldehyde from phenylalanine, which is the aldehyde moiety of Amaryllidaceae alkaloids; (3) Formation of 4′- O -methylnorbelladine from norbelladine (a condensation product of tyramine with 3,4-dihydroxybenzaldehyde); (4) Formation of unstable intermediate products by specific phenol coupling of 4′- O -methylnorbelladine followed by a reduction step; (5) Biosynthesis of the different types of Amaryllidaceae alkaloids (galanthamine, lycorine, homolycorine, galasine, haemanthamine, plicamine, secoplicamine, narciclasine, pretazettine, crinine, cripowelline, graciline, montanine, ismine, cherylline and norbelladine types, as well as galanthindole, maritinamine and elwesine). The last stage involves very specialized enzymes which could be found in different plant species producing specific Amaryllidaceae alkaloids ( Figure 2 ) [ 59 , 60 ].…”

“…PAL is a very important enzyme, since it redirects the carbon flux in the plant cell from primary to secondary metabolism, in this particular case to Amaryllidaceae alkaloid biosynthesis [ 59 , 62 , 63 ]. Several genes encoding PAL have been identified and characterized from different Amaryllidaceae species [ 58 , 59 , 60 , 64 , 65 ]. Recent phylogenetic analysis of identified Amaryllidaceae PALs showed that they can be divided into two main clusters named “PAL1” and “PAL2”, which share between 80 and 83% amino acid identities [ 59 ].…”

“…Several genes encoding PAL have been identified and characterized from different Amaryllidaceae species [ 58 , 59 , 60 , 64 , 65 ]. Recent phylogenetic analysis of identified Amaryllidaceae PALs showed that they can be divided into two main clusters named “PAL1” and “PAL2”, which share between 80 and 83% amino acid identities [ 59 ]. The transcript expression analyses of the genes from the two clusters suggest a different functional role for PAL1 versus PAL2.…”

“…The transcript expression analyses of the genes from the two clusters suggest a different functional role for PAL1 versus PAL2. It has been demonstrated that PAL1 is expressed at similar levels in all plant parts (root, bulb, stem, leaf, flower), whereas PAL2 is expressed in the bulb [ 59 , 65 , 66 ]. Another important gene from the phenylpropanoid pathway, cinnamate-4-hydroxylase (C4H), has been recently cloned and characterized to be present as a one single transcript in Amaryllidaceae alkaloid producing plants [ 59 , 60 , 64 , 65 , 67 ].…”