<i>Voacanga africana</i>: Chemistry, Quality and Pharmacological Activity

Koroch, Adolfina R.; Juliani, H. Rodolfo; Kulakowski, Daniel; Arthur, Hanson; Asante-Dartey, Juliana; Simon, James E.

doi:10.1021/bk-2009-1021.ch020

Cited by 13 publications

(22 citation statements)

References 1 publication

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“…First, by ensuring an efficient epoxidation of tabersonine (Fig. 6), it allows a controlled and easy synthesis of lochnericine, given the abundant sourcing of tabersonine (Koroch et al, 2009). Lochnericine displays cytotoxic properties against human leukemia cells in combination with other MIAs.…”

Section: Discussionmentioning

confidence: 99%

“…S7). While we succeeded previously in the synthesis of this compound through the bioconversion of hörhammericine (Carqueijeiro et al, 2018), the achievement of this production from tabersonine constitutes a marked improvement, since tabersonine can be obtained in a higher yield in plants relative to hörhammericine (Koroch et al, 2009). Furthermore, the development of such a yeast strain further enriches the toolbox dedicated to the metabolic engineering of MIAs and the capacity to achieve a tailor-made synthesis of this compound type.…”

Section: Metabolic Engineering Of the Biosynthesis Of 67-oxygenated mentioning

confidence: 91%

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Two Tabersonine 6,7-Epoxidases Initiate Lochnericine-Derived Alkaloid Biosynthesis in Catharanthus roseus

et al. 2018

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Lochnericine is a major monoterpene indole alkaloid (MIA) in the roots of Madagascar periwinkle (). Lochnericine is derived from the stereoselective C6,C7-epoxidation of tabersonine and can be metabolized further to generate other complex MIAs. While the enzymes responsible for its downstream modifications have been characterized, those involved in lochnericine biosynthesis remain unknown. By combining gene correlation studies, functional assays, and transient gene inactivation, we identified two highly conserved P450s that efficiently catalyze the epoxidation of tabersonine: tabersonine 6,7-epoxidase isoforms 1 and 2 (TEX1 and TEX2). Both proteins are quite divergent from the previously characterized tabersonine 2,3-epoxidase and are more closely related to tabersonine 16-hydroxylase, involved in vindoline biosynthesis in leaves. Biochemical characterization of TEX1/2 revealed their strict substrate specificity for tabersonine and their inability to epoxidize 19-hydroxytabersonine, indicating that they catalyze the first step in the pathway leading to hörhammericine production. and displayed complementary expression profiles, with expressed mainly in roots and in aerial organs. Our results suggest that and originated from a gene duplication event and later acquired divergent, organ-specific regulatory elements for lochnericine biosynthesis throughout the plant, as supported by the presence of lochnericine in flowers. Finally, through the sequential expression of and up to four other MIA biosynthetic genes in yeast, we reconstituted the 19-acetylhörhammericine biosynthetic pathway and produced tailor-made MIAs by mixing enzymatic modules that are naturally spatially separated in the plant. These results lay the groundwork for the metabolic engineering of tabersonine/lochnericine derivatives of pharmaceutical interest.

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Section: Discussionmentioning

confidence: 99%

Section: Metabolic Engineering Of the Biosynthesis Of 67-oxygenated mentioning

confidence: 91%

Two Tabersonine 6,7-Epoxidases Initiate Lochnericine-Derived Alkaloid Biosynthesis in Catharanthus roseus

et al. 2018

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“…In Ghana, it is locally known as 'ofruma' in the Asante language. Various plant parts are used medicinally throughout its distribution area [70]. The leaf decoction is used to treat dysentery, diarrhea, cutaneous and subcutaneous parasitic infections, leprosy, oedema, gout, paralysis and convulsion.…”

Section: Voacanga Africana Stapf (Apocynaceae)mentioning

confidence: 99%

The Ghanaian Flora as a Potential Source of Anthelmintic and Anti-Schistosomal Agents

Asante-Kwatia¹,

Mensah²,

Gyimah³

et al. 2022

Natural Medicinal Plants

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Parasitic infections including schistosomiasis and soil transmitted helminthiasis are the most commonly encountered Neglected Tropical Diseases (NTDs) in the world. These diseases remain a major public health concern affecting millions of people especially those living in poor regions where access to effective conventional health care is a challenge. Interventions to control these infections in endemic areas have not been successful due to the high cost of drugs, limited availability as well as inequity of access to preventive chemotherapies. Another problem is the development resistance to the limited number of recommended medications due to their intensive use in both human and live-stock. There is an increasing awareness of the potential of natural products as chemotherapeutic agents to combat parasitic infections. Natural products may offer an unlimited source of chemically diverse drug molecules which may be safe, efficient, less toxic, less expensive and readily available for use especially in low-income countries. The Ghanaian flora provides such a ready source for new therapeutic interventions for the local population. Several researches have provided evidence of the anti-parasitic activity of Ghanaian medicinal plants. This chapter provides a review with special focus on medicinal plants collected from Ghana with anthelmintic and anti-schistosomal activity. Evidence of pharmacological activities of crude extracts, fractions and bioactive phytoconstituents as well as possible mechanisms of action where investigated are discussed.

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“…Conceptually, the vindoline synthesis can be performed either de novo (i.e. from glucose as original carbon source) or through precursor‐directed synthesis by feeding engineered yeast with tabersonine, extractible at multigram scale from the highly abundant seeds of Voacanga africana (Kikura‐Hanajiri et al ., 2009 ; Koroch et al ., 2009 ). In this case, seven enzymatic steps are required for the biotransformation of tabersonine (Fig.…”

Section: Introductionmentioning

confidence: 99%

Enhanced bioproduction of anticancer precursor vindoline by yeast cell factories

Kulagina

Guirimand

Mélin

et al. 2021

Microbial Biotechnology

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The pharmaceutical industry faces a growing demand and recurrent shortages in many anticancer plant drugs given their extensive use in human chemotherapy. Efficient alternative strategies of supply of these natural products such as bioproduction by microorganisms are needed to ensure stable and massive manufacturing. Here, we developed and optimized yeast cell factories efficiently converting tabersonine to vindoline, a precursor of the major anticancer alkaloids vinblastine and vincristine. First, fine-tuning of heterologous gene copies restrained side metabolites synthesis towards vindoline production. Tabersonine to vindoline bioconversion was further enhanced through a rational medium optimization (pH, composition) and a sequential feeding strategy. Finally, a vindoline titre of 266 mg l À1 (88% yield) was reached in an optimized fed-batch bioreactor. This precursordirected synthesis of vindoline thus paves the way towards future industrial bioproduction through the valorization of abundant tabersonine resources.

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Voacanga africana: Chemistry, Quality and Pharmacological Activity

Cited by 13 publications

References 1 publication

Two Tabersonine 6,7-Epoxidases Initiate Lochnericine-Derived Alkaloid Biosynthesis in Catharanthus roseus

Two Tabersonine 6,7-Epoxidases Initiate Lochnericine-Derived Alkaloid Biosynthesis in Catharanthus roseus

The Ghanaian Flora as a Potential Source of Anthelmintic and Anti-Schistosomal Agents

Enhanced bioproduction of anticancer precursor vindoline by yeast cell factories

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