Lysine-derived Alkaloids: Overview and Update on Biosynthesis and Medicinal Applications with Emphasis on Quinolizidine Alkaloids

Bunsupa, Somnuk; Yamazaki, Mami; Saito, Kazuki

doi:10.2174/1389557516666160506151213

Cited by 27 publications

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“…() from various organs of Erythrochiton brasiliensis . It is also assumed that Pip is the biosynthetic precursor of indolizidine alkaloids that are formed in species of some plant families such as the Fabaceae, Asclepiadaceae, Convolvulaceae, Moraceae and Orchidaceae (Figure i) (Bunsupa et al ., ).…”

Section: Other Aspects Of Pip Metabolismmentioning

confidence: 97%

“…In some plant species, including members of the Fabaceae, Poaceae or Solanaceae families, lysine decarboxylase catalyzes the conversion of lysine to the diamine cadaverine (Tomar et al ., ; Jancewicz et al ., ). As part of the specialized metabolism in these species, cadaverine might subsequently be converted to piperidine, quinolizidine or lycopodium alkaloids (Figure ) (Bunsupa et al ., ). A lysine catabolic pathway ubiquitously present in plants, and also occurring in animals, is the saccharopine pathway, by which l ‐lysine is converted to the non‐protein dicarboxylic amino acid α‐aminoadipic acid (Aad).…”

Section: Introductionmentioning

confidence: 97%

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l‐lysine metabolism to N‐hydroxypipecolic acid: an integral immune‐activating pathway in plants

Hartmann

Zeier

2018

The Plant Journal

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l-lysine catabolic routes in plants include the saccharopine pathway to α-aminoadipate and decarboxylation of lysine to cadaverine. The current review will cover a third l-lysine metabolic pathway having a major role in plant systemic acquired resistance (SAR) to pathogen infection that was recently discovered in Arabidopsis thaliana. In this pathway, the aminotransferase AGD2-like defense response protein (ALD1) α-transaminates l-lysine and generates cyclic dehydropipecolic (DP) intermediates that are subsequently reduced to pipecolic acid (Pip) by the reductase SAR-deficient 4 (SARD4). l-pipecolic acid, which occurs ubiquitously in the plant kingdom, is further N-hydroxylated to the systemic acquired resistance (SAR)-activating metabolite N-hydroxypipecolic acid (NHP) by flavin-dependent monooxygenase1 (FMO1). N-hydroxypipecolic acid induces the expression of a set of major plant immune genes to enhance defense readiness, amplifies resistance responses, acts synergistically with the defense hormone salicylic acid, promotes the hypersensitive cell death response and primes plants for effective immune mobilization in cases of future pathogen challenge. This pathogen-inducible NHP biosynthetic pathway is activated at the transcriptional level and involves feedback amplification. Apart from FMO1, some cytochrome P450 monooxygenases involved in secondary metabolism catalyze N-hydroxylation reactions in plants. In specific taxa, pipecolic acid might also serve as a precursor in the biosynthesis of specialized natural products, leading to C-hydroxylated and otherwise modified piperidine derivatives, including indolizidine alkaloids. Finally, we show that NHP is glycosylated in Arabidopsis to form a hexose-conjugate, and then discuss open questions in Pip/NHP-related research.

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Section: Other Aspects Of Pip Metabolismmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 97%

l‐lysine metabolism to N‐hydroxypipecolic acid: an integral immune‐activating pathway in plants

Hartmann

Zeier

2018

The Plant Journal

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“…There have been many excellent general reviews of alkaloids, 16,17,19 and many detailed reviews of individual alkaloid families. 14,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] In order to differentiate this review, and to highlight its focus on the patterns in the early steps of biosynthesis, it will not be structured by alkaloid class but instead by the particular step in the aforementioned biosynthetic model (Scheme 1). By viewing alkaloid biosynthesis in this holistic manner, it may be possible to gain insights from one pathway that can be applied to aid elucidation of another.…”

Section: Patterns In Biosynthesismentioning

confidence: 99%

The scaffold-forming steps of plant alkaloid biosynthesis

Lichman

2021

Nat. Prod. Rep.

122

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“…Current synthetic methods for the formation of 1‐piperideine rely on piperidine oxidation with harsh chemicals, via N‐ chlorination and base‐mediated HCl elimination 3,4 . However, the typical route in nature for the biosynthesis of this structure is derived from lysine metabolism, where lysine is decarboxylated to cadaverine, which in turn is cyclized upon oxidation 6,7 . As a result, 1‐piperideine is a common intermediate of the biosynthesis of lysine‐derived alkaloids, such as quinolizidine, indolizidine or lycopodium alkaloids.…”

Section: Introductionmentioning

confidence: 99%

Oxidation of cadaverine by putrescine oxidase from Rhodococcus erythropolis

Anyanwu

Hall

Stephens

et al. 2021

J of Chemical Tech & Biotech

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BACKGROUND Putrescine oxidase (EC 1.4.3.10) is of interest for the microbial production of unsubstituted platform nitrogen (N‐)heterocycles, because it only requires inexpensive oxygen as co‐substrate. Putrescine oxidase from Rhodococcus erythropolis (Re‐PuO) was shown previously to catalyze the oxidation of cadaverine; however, there is little information in the literature about the robustness of this enzyme for biotechnological applications. The aim of this study was to investigate the suitability of Re‐PuO for the bioproduction of 1‐piperideine from cadaverine under different reaction conditions. RESULTS The formation of 1‐piperideine catalyzed by Re‐PuO was demonstrated using o‐aminobenzaldehyde as a reagent to trap the cyclic imine and shift the equilibrium for cyclization. A direct assay of Re‐PuO activity for cadaverine oxidation was then implemented, by monitoring oxygen consumption. Characterization of the reaction mixture by 1H NMR and mass spectrometry confirmed the presence of piperideine dimers and trimers, yet the quantification of the reaction products could not be achieved. The optimum temperature and pH conditions for enzyme activity were determined as 55 °C and 8.5, respectively. At pH 7.5, the enzyme retained its activity after 65 h incubation at 25 °C, but lost 75% of its activity after 1 h incubation at 55 °C. The enzyme showed no substrate inhibition at concentrations as high as 100 mmol L–1 cadaverine. Complete biotransformation of cadaverine was observed in whole cells at physiological conditions. CONCLUSIONS These results successfully demonstrate the potential of putrescine oxidase for the bioproduction of N‐heterocycles from cadaverine. © 2021 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).

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Lysine-derived Alkaloids: Overview and Update on Biosynthesis and Medicinal Applications with Emphasis on Quinolizidine Alkaloids

Abstract: In this review, we briefly summarize the recent understanding about the structures, occurrences, analytical procedures, biosyntheses, and potential health effects and medical applications of Lys-derived alkaloids with emphasis on quinolizidine alkaloids (QAs).

Cited by 27 publications

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l‐lysine metabolism to N‐hydroxypipecolic acid: an integral immune‐activating pathway in plants

l‐lysine metabolism to N‐hydroxypipecolic acid: an integral immune‐activating pathway in plants

The scaffold-forming steps of plant alkaloid biosynthesis

Oxidation of cadaverine by putrescine oxidase from Rhodococcus erythropolis

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