Promoting scopolamine biosynthesis in transgenic Atropa belladonna plants with pmt and h6h overexpression under field conditions

Tropane and Granatane Alkaloid Biosynthesis: A Systematic Analysis

“…TAs have been observed to attach to and inhibit muscarinic acetylcholine receptors [9]. TAs found in the Solanaceae are well known for both their anticholinergic and antispasmodic properties that affect the parasympathetic nervous system [10][11][12]. These plants have been used for pain relief, anesthesia, and as a treatment for drug addiction [10].…”

“…Hyoscyamine (4) and scopolamine (3) are the dominant TAs of H. niger and both metabolites can cross the blood-brain barrier to effect the central nervous system [17]. Scopolamine (3) has more potent pharmaceutical activity when compared to hyoscyamine (4) and exhibits relatively fewer side effects, however the scopolamine (3) content of solanaceous plants is usually much lower than the hyoscyamine (4) content [11]. Because of this, there is an ongoing effort to fully understand the biosynthesis of scopolamine (3) and other TAs within the Solanaceae (see Section 4).…”

“…Further modifications will add diverse functional groups to the core structure yielding the final end product. Ornithine (10) and arginine (11) are the amino acids predicted to be the starting substrates of TA biosynthesis (Scheme 1) [56]. Feeding studies using 14 C-proline into the roots of A. belladonna also suggest that proline (12) may be a starting amino acid for incorporation into the tropane moiety.…”

“…A one-step enzymatic approach is possible to reach a symmetrical intermediate by converting ornithine (10) into putrescine (14) catalyzed by ornithine decarboxylase (ODC) [62]. Another route to putrescine (14) can be taken by starting with the amino acid arginine (11). The decarboxylation of arginine (11) into agmatine (15) is catalyzed by arginine decarboxylase (ADC).…”

“…When both PMT and H6H were overexpressed simultaneously in transgenic H. niger root cultures, scopolamine (3) biosynthesis increased to levels over nine times more than the wild type [143]. In an important experiment testing whether metabolic engineering can occur between genes isolated from different species, overexpression of NtPMT and HnH6H in A. belladonna significantly increased scopolamine (3) content of secondary roots when compared to wild-type plants [11]. More studies are needed to understand flux through the tropane biosynthetic pathway in order to increase the overproduction of alkaloids.…”