Chemistry and biology of monoterpene indole alkaloid biosynthesis

O’Connor, Sarah E.; Maresh, Justin J.

doi:10.1039/b512615k

Cited by 912 publications

(478 citation statements)

References 183 publications

(122 reference statements)

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“…Tryptophan is thought to be a precursor for quinine biosynthesis in the tree, and these two molecules have marked structural similarity (44,45) (Fig. 7).…”

Section: Discussionmentioning

confidence: 99%

The Antimalarial Drug Quinine Disrupts Tat2p-mediated Tryptophan Transport and Causes Tryptophan Starvation

Khozoie

Pleass

Avery

2009

Journal of Biological Chemistry

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Quinine is a major drug of choice for the treatment of malaria. However, the primary mode of quinine action is unclear, and its efficacy is marred by adverse reactions among patients. To help address these issues, a genome-wide screen for quinine sensitivity was carried out using the yeast deletion strain collection. Quinine-sensitive mutants identified in the screen included several that were defective for tryptophan biosynthesis (trp strains). This sensitivity was confirmed in independent assays and was suppressible with exogenous Trp, suggesting that quinine caused Trp starvation. Accordingly, quinine was found to inhibit [ 3 H]Trp uptake by cells, and the quinine sensitivity of a trp1⌬ mutant could be rescued by overexpression of Trp permeases, encoded by TAT1 and TAT2. The site of quinine action was identified specifically as the high affinity Trp/Tyr permease, Tat2p, with which quinine associated in a Trp-suppressible manner. A resultant action also on Tyr levels was reflected by the Tyr-suppressible quinine hypersensitivity of an aro7⌬ deletion strain, which is auxotrophic for Tyr (and Phe). The present genome-wide dataset provides an important resource for discovering modes of quinine toxicity. That potential was validated with our demonstration that Trp and Tyr uptake via Tat2p is a major target of cellular quinine toxicity. The results also suggest that dietary tryptophan supplements could help to avert the toxic effects of quinine.

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“…Tryptophan is thought to be a precursor for quinine biosynthesis in the tree, and these two molecules have marked structural similarity (44,45) (Fig. 7).…”

Section: Discussionmentioning

confidence: 99%

The Antimalarial Drug Quinine Disrupts Tat2p-mediated Tryptophan Transport and Causes Tryptophan Starvation

Khozoie

Pleass

Avery

2009

Journal of Biological Chemistry

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“…The indole structure is also a building block of a multitude of synthetic compounds4 that are not only used as pharmaceutical products but are also broadly applied in various technical branches 5. The Catharanthus alkaloids and other natural monoterpene indole alkaloids are biosynthesized from tryptamine and secologanin, an iridoid glycoside, to form strictosidine 6, 7…”

Section: Introductionmentioning

confidence: 99%

Unprecedented Utilization of Pelargonidin and Indole for the Biosynthesis of Plant Indole Alkaloids

et al. 2016

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Nudicaulins are a group of indole alkaloid glycosides responsible for the color of yellow petals of Papaver nudicaule (Iceland poppy). The unique aglycone scaffold of these alkaloids attracted our interest as one of the most unusual flavonoid‐indole hybrid structures that occur in nature. Stable isotope labeling experiments with sliced petals identified free indole, but not tryptamine or l‐tryptophan, as one of the two key biosynthetic precursors of the nudicaulin aglycone. Pelargonidin was identified as the second key precursor, contributing the polyphenolic unit to the nudicaulin molecule. This finding was inferred from the temporary accumulation of pelargonidin glycosides in the petals during flower bud development and a drop at the point in time when nudicaulin levels start to increase. The precursor‐directed incorporation of cyanidin into a new 3′‐hydroxynudicaulin strongly supports the hypothesis that anthocyanins are involved in the biosynthesis of nudicaulins.

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“…[248] In this section, successful studies and milestones of transforming the alkaloid pathways in microbial platforms, especially for MIAs and BIAs production, will be described. Readers are encouraged to read other excellent reviews on alkaloids [246,249] or heterologous alkaloid production. [249b,250] …”

Section: Introductionmentioning

confidence: 99%

Metabolic Engineering of Microorganisms for the Production of Natural Compounds

Park

Yang

et al. 2017

Adv. Biosys.

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Natural products have been attracting much interest around the world for their diverse applications, especially in drug and food industries. Plants have been a major source of many different natural products. However, plants are affected by weather and environmental conditions and their successful extraction is rather limited. Chemical synthesis is inefficient due to the complexity of their chemical structures involving enantioselectivity and regioselectivity. For these reasons, an alternative means of overproducing valuable natural products using microorganisms has emerged. In recent years, various metabolic engineering strategies have been developed for the production of natural products by microorganisms. Here, the strategies taken to produce natural products are reviewed. For convenience, natural products are classified into four main categories: terpenoids, phenylpropanoids, polyketides, and alkaloids. For each product category, the strategies for establishing and rewiring the metabolic network for heterologous natural product biosynthesis, systems approaches undertaken to optimize production hosts, and the strategies for fermentation optimization are reviewed. Taken together, metabolic engineering has enabled microorganisms to serve as a prominent platform for natural compounds production. This article examines both the conventional and novel strategies of metabolic engineering, providing general strategies for complex natural compound production through the development of robust microbial‐cell factories.

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Chemistry and biology of monoterpene indole alkaloid biosynthesis

Cited by 912 publications

References 183 publications

The Antimalarial Drug Quinine Disrupts Tat2p-mediated Tryptophan Transport and Causes Tryptophan Starvation

The Antimalarial Drug Quinine Disrupts Tat2p-mediated Tryptophan Transport and Causes Tryptophan Starvation

Unprecedented Utilization of Pelargonidin and Indole for the Biosynthesis of Plant Indole Alkaloids

Metabolic Engineering of Microorganisms for the Production of Natural Compounds

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