Quinolizidine alkaloid biosynthesis

Wink, M. and Hartmann, T. 1980. Localization of enzymes of quinolizidine alkaloids biosynthesis in leaf chloroplast of Lupims polyphyllus Lindl. Plant Physiology, 70 lA-11. 

Suzuki, H., Koike, Y., Murakoshi, I. and Saito, K. 1996. Subcellular local ization of acyltransferases for quinolizidine alkaloid biosynthesis in Lupinus. Phytochemistry, 42 1557-1562. 

Hirai, M. Y., Suzuki, H., Yamazaki, M. and Saito, K. 2000. Biochemical andpatrial molecular characterization of bitter and sweet form of Lupinus angustifolius, an experimental model for study of molecular regulation of quinolizidine alkaloids biosynthesis. Chemistry and Pharmacy. Bulletin, 48 1458-1461. 

Quinolizidine Alkaloids.—Biosynthesis of quinolizidine alkaloids, e.g. sparteine (28), is from lysine (15) by way of cadaverine (16), as shown in Scheme 4. Three cadaverine units (as indicated by the thickened bonds) are required for the construction of alkaloids such as sparteine (28).10 Although something has been discerned about the biosynthetic relationships of various quinolizidine alkaloids, the nature of early intermediates beyond cadaverine has remained quite elusive.10 Exciting new results obtained with crude enzyme preparations from cell suspension cultures of Lupinus polyphyllus indicate why this is so. 

Unique subcellular compartmentation is also present in quinolizidine alkaloid biosynthesis, which occurs in the mesophyll chloroplasts of some legumes.158 One of the enzymes catalyzing the last two acylations of the pathway in Lupinus albus occurs in the cytoplasm, whereas the other resides in the mitochondria/59 Although the quinolizidine nucleus appears to be synthesized in the chloroplast, subsequent modifications can occur only after alkaloid intermediates are transported to the cytosol and mitochondia. Quinolizidine alkaloids appear to accumulate in vacuoles of epidermal cells where their defensive properties are most effective. 

WINK, M., HARTMANN, T., Localization of the enzymes of quinolizidine alkaloid biosynthesis in leaf chloroplasts of Lupinus polyphyllus. Plant Physiol., 1982, 70, 74-77. 

Wink, M. and Witte, L. (1983) Evidence for a widespread occurrence of the genes of quinolizidine alkaloid biosynthesis. FEBS Lett., 159,196-200. 

Report, p. 14). Curiously, the nature of the intermediates in quinolizidine alkaloid biosynthesis is unknown, although an attractive hypothesis has been proposed that is based on incorporation of A -piperideine (3). ... 

The biochemistry and molecular biology of quinolizidine alkaloid biosynthesis have not been fully characterized. Quinolizidine alkaloids are formed from lysine via lysine decarboxylase (LDC), where cadaverine is the first detectable intermediate (Scheme 6). Biosynthesis of the quinolizidine ring is thought to arise from the cyclization of cadaverine units via an enzyme-bound intermediate 176). LDC and the quinolizidine skeleton-forming enzyme have been detected in chlorop-lasts of L. polyphyllus 177). Once the quinolizidine skeleton has been formed, it is modified by dehydrogenation, hydroxylation, or esterification to generate the diverse array of alkaloid products. 

Human Poisoning by Pyrrolizidine Alkaloids Medicinal Uses of Pyrrolizidine Alkaloids Quinolizidine Alkaloids Biosynthesis... 

Fig. 30.8 (a b). Labeling studies for quinolizidine alkaloid biosynthesis (modified from Herbert, 1988 and Spenser, 1985 used with permission of the copyright owners. The Royal Society of Chemistry, Cambridge and the International Union of Pure and Applied Chemistry, Oxford, respectively). 

The discovery of the indolizidine alkaloid swainsonine (35) and its A-oxide (37) in the leguminous gtn tdi Astragalus, Oxytropis, and Swainsona suggests a biosynthetic route somewhat resembling those of pyrrolizidine and quinolizidine alkaloid biosynthesis (Harris et al, 1987 Kinghom and Balandrin, 1984). The similarity of certain indolizidine alkaloids to coniine-related compounds, such as 8-coniceine (not naturally occurring) has been observed. 

Wink, M. and T. Hartmann, Enzymology of quinolizidine alkaloid biosynthesis, in Natural Products Chemistry 1984 (14th lUPAC Symposium on the Chemistry of Natural Products) (R, I. Zalewski and J. J. Skolik, eds.), Elsevier, Amsterdam, 1984. 

Bunsupa S, Katayama K, Dcerrra E, Oikawa A, Toyooka K, Saito K, Yamazaki M (2012) Lysine decarboxylase catalyzes the first step of quinolizidine alkaloid biosynthesis and coevolved with alkaloid production in leguminosae. Plant Cell 24 1202-1216 Facchini PJ (2001) Alkaloid biosynthesis in plants biochemistry, cell biology, molecular regulation, and metabolic engineering applications. Annu Rev Plant Physiol Plant Mol Biol 52 29-66... 

Wink M, Hartmatm T (1985) Enzymology of quinolizidine alkaloid biosynthesis. In Zalewski RI, Skolik JJ (eds) Natural products cherrristry. Elsevier, Amsterdam, pp 511-520... 

Quinolizidine alkaloid biosynthesis Cadaverine, (+)-P- coumaioylepilupinine/lupinine, (—)-13a-tigloyloxymuttflOTme/lupanine... 

Suzuki H, Koike Y, Murakoshi I, et al. (1996) Subcellular localization of acyltransferases for quinolizidine alkaloid biosynthesis in Lupinus. Phytochemistry 42 1557-1562 Taguchi G, Fujikawa S, Yazawa T, et al. (2000) Scopoletin uptake from culture medium and accumulation in the vacuoles after conversion to scopolin in 2,4-D-treated tobacco cells. Plant Sci 151 153-161... 

Light may also r ulate PA conjugate formation in ehloroplasts of Chinese cabbage (S. S. Cohen etal., 1982), as well as quinolizidine alkaloid biosynthesis in ehloroplasts of Lupinus (Wink, 1985). Since the biosynthesis of putrescine-derived alkaloids occurs mainly in the root (Dawson, 1942), one could speculate that their formation might also be r ulated by hght. 

Enzymes of Quinolizidine Alkaloid Biosynthesis.- In the past four years Hartmann, Wink, and their coworkers have obtained enzymes from Lupinus (especially L.polyphyllus) species which catalyse the formation of the tetracyclic quinolizidine alkaloids such as sparteine and lupanine from lysine. A novel biogenetic scheme has been proposed which accommodates these new results, and is consistent with previous biosynthetic studies on these alkaloids in intact plants . This new hypothesis (with some minor modifications by this reporter) is illustrated in Scheme 4. The first step in this sequence is the decarboxylation of lysine to yield cadaverine (38). This lysine decarboxylase was isolated from the chloroplasts of L. polyphyHub lea.ves, It is also present in... 

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