Trends for diverse production strategies of plant medicinal alkaloids

Abstract

Covering: 1999 to 2009

Alkaloids represent a large and highly diverse group of low-molecular-weight compounds related only by the presence of a nitrogen atom in a heterocyclic ring, and are organized into groups according to the structure of their carbon skeleton. Alkaloids are predominantly derived from amino acids and are found in approximately 20% of plant species. As secondary metabolites, alkaloids are thought to play a defensive role in providing protection for the plant against herbivores and pathogens. Due to their potent biological activity, many of the approximately 20 000 known alkaloids have been exploited as pharmaceuticals, stimulants, narcotics and poisons. Plant-derived alkaloids that are currently in clinical use include the anti-neoplastic agents vinblastine and vincristine, the analgesics morphine and codeine, the anti-hypertensives ajmalicine and serpentine, the anti-arrhythmic ajmaline, the muscle relaxants (+)-tubocurarine and papaverine, and the sedative scopolamine. Other well-known plant alkaloids include caffeine, cocaine and nicotine. Within the plant cell culture experimental system, molecular and structural biology techniques have allowed the application of enzymatic engineering strategies to attempt to improve medicinal alkaloids, through the exploration of metabolic engineering of biosynthetic pathways to create new ‘natural’ alkaloids that can be used for structure–activity relationship studies.