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Reconstitution of monoterpene indole alkaloid biosynthesis in genome engineered Nicotiana benthamiana
by
Sherden, Nathaniel H.
, Patron, Nicola J.
, Chhetry, Monika
, Jo, Seohyun
, Guerrero, Delia Ayled Serna
, O’Connor, Sarah E.
, Dudley, Quentin M.
, Smedley, Mark A.
, Caputi, Lorenzo
, Harwood, Wendy A.
in
38/22
/ 42
/ 42/41
/ 42/44
/ 45/91
/ 631/449/2667
/ 631/61/318
/ Alkaloids
/ Biology
/ Biomedical and Life Sciences
/ Biosynthesis
/ Enzymes
/ Genomes
/ Glycosyltransferases - genetics
/ Indole Alkaloids - metabolism
/ Indoles
/ Intermediates
/ Latex
/ Life Sciences
/ Medicinal plants
/ Metabolic flux
/ Metabolism
/ Monoterpenes
/ Natural products
/ Nicotiana - genetics
/ Nicotiana - metabolism
/ Nicotiana benthamiana
/ Plants - metabolism
/ Transcriptomics
2022
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Reconstitution of monoterpene indole alkaloid biosynthesis in genome engineered Nicotiana benthamiana
by
Sherden, Nathaniel H.
, Patron, Nicola J.
, Chhetry, Monika
, Jo, Seohyun
, Guerrero, Delia Ayled Serna
, O’Connor, Sarah E.
, Dudley, Quentin M.
, Smedley, Mark A.
, Caputi, Lorenzo
, Harwood, Wendy A.
in
38/22
/ 42
/ 42/41
/ 42/44
/ 45/91
/ 631/449/2667
/ 631/61/318
/ Alkaloids
/ Biology
/ Biomedical and Life Sciences
/ Biosynthesis
/ Enzymes
/ Genomes
/ Glycosyltransferases - genetics
/ Indole Alkaloids - metabolism
/ Indoles
/ Intermediates
/ Latex
/ Life Sciences
/ Medicinal plants
/ Metabolic flux
/ Metabolism
/ Monoterpenes
/ Natural products
/ Nicotiana - genetics
/ Nicotiana - metabolism
/ Nicotiana benthamiana
/ Plants - metabolism
/ Transcriptomics
2022
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Reconstitution of monoterpene indole alkaloid biosynthesis in genome engineered Nicotiana benthamiana
by
Sherden, Nathaniel H.
, Patron, Nicola J.
, Chhetry, Monika
, Jo, Seohyun
, Guerrero, Delia Ayled Serna
, O’Connor, Sarah E.
, Dudley, Quentin M.
, Smedley, Mark A.
, Caputi, Lorenzo
, Harwood, Wendy A.
in
38/22
/ 42
/ 42/41
/ 42/44
/ 45/91
/ 631/449/2667
/ 631/61/318
/ Alkaloids
/ Biology
/ Biomedical and Life Sciences
/ Biosynthesis
/ Enzymes
/ Genomes
/ Glycosyltransferases - genetics
/ Indole Alkaloids - metabolism
/ Indoles
/ Intermediates
/ Latex
/ Life Sciences
/ Medicinal plants
/ Metabolic flux
/ Metabolism
/ Monoterpenes
/ Natural products
/ Nicotiana - genetics
/ Nicotiana - metabolism
/ Nicotiana benthamiana
/ Plants - metabolism
/ Transcriptomics
2022
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Reconstitution of monoterpene indole alkaloid biosynthesis in genome engineered Nicotiana benthamiana
Journal Article
Reconstitution of monoterpene indole alkaloid biosynthesis in genome engineered Nicotiana benthamiana
2022
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Overview
Monoterpene indole alkaloids (MIAs) are a diverse class of plant natural products that include a number of medicinally important compounds. We set out to reconstitute the pathway for strictosidine, a key intermediate of all MIAs, from central metabolism in
Nicotiana benthamiana
. A disadvantage of this host is that its rich background metabolism results in the derivatization of some heterologously produced molecules. Here we use transcriptomic analysis to identify glycosyltransferases that are upregulated in response to biosynthetic intermediates and produce plant lines with targeted mutations in the genes encoding them. Expression of the early MIA pathway in these lines produces a more favorable product profile. Strictosidine biosynthesis was successfully reconstituted, with the best yields obtained by the co-expression of 14 enzymes, of which a major latex protein-like enzyme (MLPL) from Nepeta (catmint) is critical for improving flux through the iridoid pathway. The removal of endogenous glycosyltransferases does not impact the yields of strictosidine, highlighting that the metabolic flux of the pathway enzymes to a stable biosynthetic intermediate minimizes the need to engineer the endogenous metabolism of the host. The production of strictosidine
in planta
expands the range of MIA products amenable to biological synthesis.
The biosynthesis of strictosidine, a key intermediate of monoterpene indole alkaloids, was successfully reconstructed in Nicotiana benthamiana, demonstrating the potential of Nicotiana benthamiana as a bioproduction chassis for small molecules.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 42
/ 42/41
/ 42/44
/ 45/91
/ Biology
/ Biomedical and Life Sciences
/ Enzymes
/ Genomes
/ Glycosyltransferases - genetics
/ Indole Alkaloids - metabolism
/ Indoles
/ Latex
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