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Strategies for the in vitro production of antiaddictive ibogan type alkaloids from Apocynaceae species

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Abstract

Monoterpenoid indole alkaloids (MIAs) of the ibogan type, such as ibogaine, have shown promising antiaddictive effects against several drugs of abuse in humans and animal models of addiction. Unfortunately, international ibogaine demand has led to the overexploitation of natural populations of the African species Tabernanthe iboga (Apocynaceae), the main source of this alkaloid. Therefore, it is necessary to identify alternative ibogan type alkaloid-containing plant species, as well as to develop new sustainable production systems for said group of pharmaceutically important compounds. In this review, we focus on strategies for the in vitro production of the antiaddictive ibogan type MIAs coronaridine, ibogamine, voacangine, and ibogaine (collectively named “CIVI-complex”) from Apocynaceae species, with particular emphasis on the Tabernaemontana genus. Since plant tissue culture (PTC)-related information on the CIVI-complex is scarce, we also consider reports on the in vitro production of other ibogan type MIAs and where necessary, of compounds belonging to the aspidospermatan, corynanthean, and plumeran type.

Key message

This review aims at giving an overview of potential strategies to produce antiaddictive ibogan type alkaloids from in vitro cultures of Apocynaceae species.

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Abbreviations

2,4-D:

2,4-dichlorophenoxyacetic acid

7-DLGT:

7-deoxyloganetic acid glucosyltransferase

7-DLH:

7-deoxyloganic acid hydroxylase

8-HGO:

8-hydroxygeraniol oxidoreductase

ASO:

O-acetylstemmadenine oxidase

BA:

Benzyladenine

CC:

Callus culture

CCC:

Compact callus cluster

CIVI:

Coronaridine-ibogamine-voacangine-ibogaine

CNS:

Central nervous system

CSC:

Cell suspension culture

G8O:

Geraniol-8-oxidase

GDNF:

Glial cell line-derived neurotrophic factor

GES:

Geraniol synthase

G(G)PPS:

Geranyl(geranyl) diphosphate synthase

GO:

Geissoschizine oxidase

GS:

Geissoschizine synthase

HL1:

Hydrolase 1

HRC:

Hairy root culture

I10H:

Ibogamine 10-hydroxylase

IAA:

Indoleacetic acid

IBA:

Indolebutyric acid

IO:

Iridoid oxidase

IPAP:

Internal phloem-associated parenchyma

IS:

Iridoid synthase

JA:

Jasmonic acid

LAMT:

Loganic acid-O-methyltransferase

MeJA:

Methyl jasmonate

MEP:

Methylerythritol phosphate

MIA:

Monoterpenoid indole alkaloid

N10OMT:

Noribogaine-10-O-methyltransferase

NAA:

1-Naphthaleneacetic acid

NMDA:

N-methyl-D-aspartate

PGR:

Plant growth regulator

PTC:

Plant tissue culture

SA:

Salicylic acid

SAR:

Systemic acquired resistance

SAT:

Stemmadenine O-acetyltransferase

SGD:

Strictosidine β-glucosidase

SLS:

Secologanin synthase

STR:

Strictosidine synthase

TDC:

Tryptophan decarboxylase

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Acknowledgements

The figure included in this article was created using ChemBioDraw Ultra 13.0 (vector). This work was supported by the Posgrado en Ciencias Biológicas, UNAM, in the context of the first author’s doctoral studies. Felix Krengel received a scholarship from the Consejo Nacional de Ciencia y Tecnología (CONACYT) (Beca Nacional para Estudios de Posgrado, No. 429281; CVU/Becario No. 545330/292756).

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Authors and Affiliations

  1. Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, Av. Universidad 3000, 04360, Delegación Coyoacán, Ciudad de México, Mexico

    Felix Krengel

  2. Instituto de Química, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, Av. Universidad 3000, Circuito Exterior S/N, 04510, Delegación Coyoacán, Ciudad de México, Mexico

    Felix Krengel & Ricardo Reyes-Chilpa

  3. Facultad de Química, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, Av. Universidad 3000, Circuito Exterior S/N, 04510, Delegación Coyoacán, Ciudad de México, Mexico

    Teresa de Jesús Olivera-Flores

  4. Facultad de Ciencias, Universidad Nacional Autónoma de México (UNAM), Ciudad Universitaria, Av. Universidad 3000, Circuito Exterior S/N, 04510, Delegación Coyoacán, Ciudad de México, Mexico

    Josefina Herrera-Santoyo

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  1. Felix Krengel
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  2. Teresa de Jesús Olivera-Flores
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  3. Josefina Herrera-Santoyo
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  4. Ricardo Reyes-Chilpa
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Contributions

FK, TOF, and JHS conducted the literature survey. FK wrote the draft. Based on the comments of all authors, FK and RRC wrote the final version of the manuscript.

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Correspondence to Ricardo Reyes-Chilpa.

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Communicated by Danny Geelen.

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Krengel, F., Olivera-Flores, T.d.J., Herrera-Santoyo, J. et al. Strategies for the in vitro production of antiaddictive ibogan type alkaloids from Apocynaceae species. Plant Cell Tiss Organ Cult 138, 215–227 (2019). https://doi.org/10.1007/s11240-019-01629-z

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