Fields are alive with the promise of medicine. Consider my list of dozen alkaloids found in nature. They exist in whole plant or its organ(s). Some of these chemical compounds are in minute amounts. For example, vincristine, the cancer chemotherapeutic compound in Catharanthus roseus, occurs at concentrations under 0.0003% on a dry basis. The root of Strychnos nux-vomica contains about 6% strychnine, a pesticide and a former stimulant.[1] 
Papaveraceae
Credit: Jean-Pol GRANDMONT
List of Pharmaceutical applications: Alkaloid/type (organ, source plant):
Anti-arrhythmic: Ajmaline/MIA (root, Rauwolfia sellowii), Quinidine/MIA (bark, Cinchona ledgeriana)
Antibacterial (in dental products): Sanguinarine/BIA (root, Sanguinaria canadiensis)
Antihypertensive: Reserpine/MIA (root, Rauwolfia nitida)
Antimalarial, analgesic: Quinine/MIA (bark, Cinchona ledgeriana)
Antimicrobial: Berberine/BIA (root, Berberis vulgaris)
Chemotherapeutics: Camptothecin/MIA (bark, Camptotheca acuminata), Vinblastine/MIA (whole plant, Catharanthus roseus), Vincristine/MIA (whole plant, Catharanthus roseus)
Erectile dysfunction treatment: Yohimbine/MIA (bark, Pausinystalia yohimbe)
Pesticide: Strychnine/MIA (root, Strychnos nux-vomica)
Vasodilator: Papaverine/BIA (seed, Papaver somniverum)
where BIA and MIA stand for benzylisoquinoline alkaloids and monoterpenoid indole alkaloids, respectively. They are two subclasses out of four that include also tropane and purine alkaloids.[1]
Alkaloids are chemical compounds that contain basic nitrogen atoms. About 10,000 plant alkaloids have been identified for many pharmacological activities. In the current view, as expressed by Effendi Leonard et al, alkaloids are mostly involved in plant defense against pathogens, insects, and herbivores. Their potent toxicity makes alkaloids "priviledged" structures for drug development.
For purposes of biosynthesis, the authors examine all alkaloids under four subclasses: the benzylisoquinoline, monoterpenoid indole, tropane, and purine alkaloids. Benzylisoquinoline alkaloids (BIA) are derived from tyrosine and are comprised of approximately 2,500 defined structures found mainly in the Papaveraceae (see photo), Ranunculaceae, Berberidaceae, and Menispermaceae.
The monoterpenoid indole alkaloids (MIA) are derived from tryptophan metabolism and are considered to be some of the most structurally diverse natural products. With over 2,000 structures, they are mainly found in the Apocynaceae, Loganiaceae, and Rubiaceae. Tropane alkaloids are the third subclass whose members are found primarily in the Solanaceae. The fourth subclass is derived from purine nucleotides instead of amino acids. An example of a purine alkaloid is caffeine, whose biosynthetic pathways have been researched in Camellia, Coffea, Theobroma, and Ilex (see photo).
Ilex (A holly bush with a lone red cherry in winter. Credit: Hari Menon)
Scheme 1 describes the general biosynthetic schemes of BIA and MIA alkaloid subclasses. Some important alkaloid products are represented.: (a) BIA (NCS, norcoclaurine synthase) and (b) MIA (TDC, tryptophan decarboxylase; STR, strictosidine synthase). In addition, the paper describes biosynthesis of tropane and purine alkaloids. "The lack of complete understanding of the complex alkaloid biosynthetic networks also hinders the determination of an effective metabolic engineering strategy to achieve a specific production phenotype" say the authors.
Scheme 1 - The general biosynthetic schemes of BIA and MIA alkaloid subclasses. Some important alkaloid products are represented. (a) BIA (NCS, norcoclaurine synthase). (b) MIA (TDC, tryptophan decarboxylase; STR, strictosidine synthase). [1]
Also taken from Effendi Leonard et al is Figure 1. This compares the relative complexities of plant and microbial systems. "Because the characteristics and metabolic capacities of plant cell/tissue and microbial systems are inherently different, they can serve as complementary unit operations in order to solve the long-standing problem of robust alkaloid production."
Also taken from Effendi Leonard et al is Figure 1. This compares the relative complexities of plant and microbial systems. "Because the characteristics and metabolic capacities of plant cell/tissue and microbial systems are inherently different, they can serve as complementary unit operations in order to solve the long-standing problem of robust alkaloid production."
The authors discuss many opportunities and challenges of implementing metabolic engineering for synthesis of natural and unnatural plant alkaloids. Their literature survey includes 96 publications.
Certainly, mathematical modeling in plant metabolic engineering can aid in determining optimum production strategies.
Reference
[1] Effendi Leonard, Weerawat Runguphan, Sarah O'Connor&Kristala Jones Prather. Opportunities in metabolic engineering to facilitate scalable alkaloid production. Nature Chemical Biology 5, 292 - 300 (2009) Published online: 17 April 2009
doi :10.1038/nchembio.160
doi :10.1038/nchembio.160
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