Cultivation of tropane alkaloid producing plants

Commercial cultivation of
Duboisia spp. in Australia, Erythroxylum spp. in South America, and Hyoscyamus muticus in Egypt, constitutes the basis for supply of the global demand for tropane alkaloids. Also to a limited extent, Hyoscyamus niger is cultivated in USA, UK and India; Atropa belladonna is cultivated in UK, Germany, former USSR, USA and India; and Duboisia spp. are cultivated in India and Ecuador. While the Scopolia spp. are collected from wild sources in China and Romania.

Fig. Commercial cultivation1, Semi-commercial cultivation2, and wild sources3 of tropane alkaloid producing plants

Hairy root culture, a Biotechnological approach towards efficient alkaloid production, is also in progress for commercialization (along with some technical limitation), e.g. Agrobacterium rhizogenes induced hairy root culture of Hyoscyamus muticus.

Fig.  Hairy root culture of Hyoscyamus muticus Courtesy Annika Wilhelmson

Coca cultivation:

The sources of all cultivated coca are two closely related South American shrub species Erythroxylum coca and Erythroxylum novogranatense (Plowman, 1984) adapted to environmentally distinct regions in Colombia, Bolivia, Peru (Ehleringer, 2000) and, most recently, Brazil (Duffy, 2008). Each species has an additional variety, E. coca var. ipadu and E. novogranatense var. truxillense, with the former known for its traditional use by lowland Amazonian groups (Plowman 1981) and the latter a drought resistant variety grown largely for commercial purposes in arid to semi-arid inter Andean valleys. Although E. coca var. ipadu has been cultivated in lowland Amazonia for many centuries, historically, its low alkaloid content has made it a poor choice for cocaine production; nevertheless, recent research on coca cultivated illegally in the Colombian Amazon indicates farmers to be increasingly cultivating high producing hybrids of E. coca var. ipadu (Johnson, 2003). These hybrids would be well adapted and easily diffused to other parts of the Amazon (Duffy 2008).

Fig. A coca farm

Duboisia cultivation:

Duboisia are native to the Kingaroy district of Queensland, Australia. In 1940 collection of Duboisia from the wild commenced. Commercial production of scopolamine began in 1941, that of hyoscyamine /atropine in 1942 (Barnard 1952). Propagation of plants and plantations was limited in the early years due to the abundance of naturally occurring trees when land was cleared and burnt. For the harvest of Duboisia leaf for extraction, the trees are cut, the complete branches with the leaves are air dried and then the dry leaves removed (traditional method), or the fresh branches are chopped, the leaf separated from the wood chips and dried artificially (common industrial method). The stumps normally regrow and can be harvested again after about 12 months. The first large- scale plantations did not occur until the late 1950s, and then they were mainly from seedlings transplanted from natural germination in the wild.

Plant-related research initially focused on plant propagation, on identification of alkaloid-rich genotypes, and the elucidation of the reasons of alkaloid variation (Barnard and Finnemore 1945). These activities gained a new dimension when, in the area where the habitats of D. myoporoides and D. leichhardtii overlap, intermediate types were found that appeared to be natural interspecific hybrids. Artificial hybridization experiments started, and by 1945 the first hybrid plants were established in the field (Groszman 1949; Hills 1954). After the end of World War II, commercial alkaloid extraction and government-supported research continued until about 1954 when the export embargo on Duboisia leaf was lifted. Commercial extraction was no longer competitive in the international market; research was considerably reduced if not ceased. Exportation ofDuboisia leaf from collection of wild material and increasingly from cultivation commenced and continued with a steadily growing level, one of the main buyers being Boehringer Ingelheim.

In 1976 Boehringer Ingelheim has established its own Duboisia plantations within coastal forests from southern New South Wales to Northern Queensland. Since then the company has acquired several other properties, bringing the total acreage of our properties to around 990 hectares. The leaf of the Duboisia tree is harvested, dried and packaged in Australia, and then shipped to the Chemicals division of Boehringer Ingelheim in Germany, where extraction of active ingredients takes place. Today Boehringer Ingelheim, the manufacturer of Buscopan, is the world's leading producer of Duboisia, delivering 90% of the global requirement of the ingredient in 2010s.