The Amaryllidaceae alkaloids: biosynthesis and methods for enzyme discovery

Kilgore, Matthew B.; Kutchan, Toni M.

doi:10.1007/s11101-015-9451-z

Cited by 69 publications

(45 citation statements)

References 160 publications

(189 reference statements)

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“…124 These related alkaloids are all multicyclic compounds derived from L-Phe and L-Tyr, and go through a common intermediate norbelladine. 125 Following O- methylation by a specific methyltransferase to give 4- O′ -methylnorbelladine ( 121 ) 126 , a P450 is suggested to initiate phenolic coupling by hydrogen abstraction from the B ring. Delocalization of the radical on the ortho and para positions of the ring can lead to different coupling regioselectivity as shown in Scheme 23.…”

Section: Radical Cyclization Mechanismsmentioning

confidence: 99%

Oxidative Cyclization in Natural Product Biosynthesis

et al. 2016

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Oxidative cyclizations are important transformations that occur widely during natural product biosynthesis. The transformations from acyclic precursors to cyclized products can afford morphed scaffolds, structural rigidity and biological activities. Some of the most dramatic structural alterations in natural product biosynthesis occur through oxidative cyclization. In this review, we examine the different strategies used by Nature to create new intra-(inter-)-molecular bonds via redox chemistry. The review will cover both oxidation- and reduction-enabled cyclization mechanisms, with an emphasis on the former. Radical cyclizations catalyzed by P450, nonheme iron, α-KG dependent oxygenases and radical SAM enzymes are discussed to illustrate the use of molecular oxygen and S-adenosylmethionine to forge new bonds at unactivated sites via one-electron manifolds. Nonradical cyclizations catalyzed by flavin-dependent monooxygenases and NAD(P)H-dependent reductases are covered to show the use of two-electron manifolds in initiating cyclization reactions. The oxidative installation of epoxides and halogens into acyclic scaffolds to drive subsequent cyclizations are separately discussed as examples of “disappearing” reactive handles. Lastly, oxidative rearrangement of rings systems, including contractions and expansions will be covered.

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Section: Radical Cyclization Mechanismsmentioning

confidence: 99%

Oxidative Cyclization in Natural Product Biosynthesis

et al. 2016

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“…The optimization of Amaryllidaceae alkaloid accumulation using in vitro cultures requires an understanding of their biosynthetic pathway. Although, to date, little is known on the genetic level (only one gene has been identified [17]), the reactions involved in this biosynthetic pathway, along with the Amaryllidaceae alkaloid common precursor [5,[17][18][19][20][21][22]. The influence of several in vitro culture conditions on Amaryllidaceae alkaloid biosynthesis has been also studied.…”

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confidence: 99%

Stimulating effect of both 4’‐O‐methylnorbelladine feeding and temporary immersion conditions on galanthamine and lycorine production by Leucojum aestivum L. bulblets

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Ptak

Boisbrun

et al. 2016

Engineering in Life Sciences

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Bulb cultures of Leucojum aestivum and L. aestivum 'Gravety Giant' were subcultured in medium containing the precursor 4'-O-methylnorbelladine (MN) at various concentrations [0 (control), 0.15 and 0.3 g/L]. The cultures were conducted in bioreactor RITA R and lasted for 15, 30, 40 and 50 days. The growth rate and the alkaloid accumulation in bulblets were studied. For this latter purpose, a purification method was developed. It comprised a highly selective solid phase extraction using on the one hand, UPTI-CLEAN SI and SCX cartridges for plant extracts and on the other hand, 2H cartridges for culture media. Pure alkaloidal fractions were, thus, analyzed by LC-ESI-MS allowing the quantitative evaluation of galanthamine and lycorine from culture extracts. Precursor feeding along with temporary immersion conditions was found to significantly improve the accumulation of both galanthamine and lycorine. The maximal concentrations of galanthamine (0.81 mg/g DW) and lycorine (0.54 mg/g DW) in L. aestivum bulblets were reached, respectively, after 40 days of culture with 0.15 g/L of precursor and after 30 days of culture with 0.3 g/L of precursor. In L. aestivum 'Gravety Giant' bulb cultures, 0.3 g/L of precursor was the best condition for both galanthamine (0.6 mg/g DW after 50 days) and lycorine (1.13 mg/g DW after 30 days).

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“…Some noteworthy exceptions are the collection of alkaloids that have been found in the genus Hosta, which is in the order Asparagales, along with Amaryllidaceae [12]. Amaryllidaceae alkaloids are derived from the aromatic acids phenyalanine and tyrosine, which are used to produce key intermediates in the biosynthesis of the AA 4 -O-methylnorbelladine [13]. According to the name of this key intermediate, this biosynthetic pathway of AA is called the norbelladine pathway.…”

Section: Introductionmentioning

confidence: 99%

“…N. filifolia was examined for its alkaloidal constituents [16], and, following the usual extractive and chromatographic procedures, eight alkaloids, as well as phenol, were isolated. The known compounds belladine (1), 11-O-acetylambelline (9), and undulatine (26) were isolated as the main compounds, in addition to the minor components: Ambelline (7) and 6α-hydroxybuphandrine (13). N-Demethylbelladine (4), 6α-methoxybuphandrine (14) and filifoline (22, the 11-O-nicotinyl analogue of ambelline) were reported for the first time as natural products.…”

Section: Introductionmentioning

confidence: 99%

The Genus Nerine Herb. (Amaryllidaceae): Ethnobotany, Phytochemistry, and Biological Activity

et al. 2019

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Nerine Herbert, family Amaryllidaceae, is a genus of about 30 species that are native to South Africa, Botswana, Lesotho, Namibia, and Swatini (formerly known as Swaziland). Species of Nerine are autumn-flowering, perennial, bulbous plants, which inhabit areas with summer rainfall and cool, dry winters. Most Nerine species have been cultivated for their elegant flowers, presenting a source of innumerable horticultural hybrids. For many years, species of Nerine have been subjected to extensive phytochemical and pharmacological investigations, which resulted in either the isolation or identification of more than fifty Amaryllidaceae alkaloids belonging to different structural types. Amaryllidaceae alkaloids are frequently studied for their interesting biological properties, including antiviral, antibacterial, antitumor, antifungal, antimalarial, analgesic, cytotoxic, and cholinesterase inhibition activities. The present review aims to summarize comprehensively the research that has been reported on the phytochemistry and pharmacology of the genus Nerine.

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The Amaryllidaceae alkaloids: biosynthesis and methods for enzyme discovery

Cited by 69 publications

References 160 publications

Oxidative Cyclization in Natural Product Biosynthesis

Oxidative Cyclization in Natural Product Biosynthesis

Stimulating effect of both 4’‐O‐methylnorbelladine feeding and temporary immersion conditions on galanthamine and lycorine production by Leucojum aestivum L. bulblets

The Genus Nerine Herb. (Amaryllidaceae): Ethnobotany, Phytochemistry, and Biological Activity

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