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Saccharomyces Cerevisiae-An Interesting Producer of Bioactive Plant Polyphenolic Metabolites.

ABSTRACT: Secondary phenolic metabolites are defined as valuable natural products synthesized by different organisms that are not essential for growth and development. These compounds play an essential role in plant defense mechanisms and an important role in the pharmaceutical, cosmetics, food, and agricultural industries. Despite the vast chemical diversity of natural compounds, their content in plants is very low, and, as a consequence, this eliminates the possibility of the production of these interesting secondary metabolites from plants. Therefore, microorganisms are widely used as cell factories by industrial biotechnology, in the production of different non-native compounds. Among microorganisms commonly used in biotechnological applications, yeast are a prominent host for the diverse secondary metabolite biosynthetic pathways. Saccharomyces cerevisiae is often regarded as a better host organism for the heterologous production of phenolic compounds, particularly if the expression of different plant genes is necessary.

SUBMITTER: Chrzanowski G

PROVIDER: S-EPMC7582661 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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<i>Saccharomyces Cerevisiae</i>-An Interesting Producer of Bioactive Plant Polyphenolic Metabolites.

Chrzanowski Grzegorz G

International journal of molecular sciences 20201005 19

Secondary phenolic metabolites are defined as valuable natural products synthesized by different organisms that are not essential for growth and development. These compounds play an essential role in plant defense mechanisms and an important role in the pharmaceutical, cosmetics, food, and agricultural industries. Despite the vast chemical diversity of natural compounds, their content in plants is very low, and, as a consequence, this eliminates the possibility of the production of these interes ...[more]

PMID: 33027901

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Project description:Monoterpene indole alkaloids (MIAs) are a class of natural products comprised of thousands of structurally unique bioactive compounds with significant therapeutic values. Due to difficulties associated with isolation from native plant species and organic synthesis of these structurally complex molecules, microbial production of MIAs using engineered hosts are highly desired. In this work, we report the engineering of fully integrated Saccharomyces cerevisiae strains that allow de novo access to strictosidine, the universal precursor to thousands of MIAs at 30-40 mg/L. The optimization efforts were based on a previously reported yeast strain that is engineered to produce high titers of the monoterpene precursor geraniol through compartmentalization of mevalonate pathway in the mitochondria. Our approaches here included the use of CRISPR-dCas9 interference to identify mitochondria diphosphate transporters that negatively impact the titer of the monoterpene, followed by genetic inactivation; the overexpression of transcriptional regulators that increase cellular respiration and mitochondria biogenesis. Strain construction included the strategic integration of genes encoding both MIA biosynthetic and accessory enzymes into the genome under a variety of constitutive and inducible promoters. Following successful de novo production of strictosidine, complex alkaloids belonging to heteroyohimbine and corynantheine families were reconstituted in the host with introduction of additional downstream enzymes. We demonstrate that the serpentine/alstonine pair can be produced at ∼5 mg/L titer, while corynantheidine, the precursor to mitragynine can be produced at ∼1 mg/L titer. Feeding of halogenated tryptamine led to the biosynthesis of analogs of alkaloids in both families. Collectively, our yeast strain represents an excellent starting point to further engineer biosynthetic bottlenecks in this pathway and to access additional MIAs and analogs through microbial fermentation.One sentence summaryAn Saccharomyces cerevisiae-based microbial platform was developed for the biosynthesis of monoterpene indole alkaloids, including the universal precursor strictosidine and further modified heteroyohimbine and corynantheidine alkaloids.

Dataset Information

Saccharomyces Cerevisiae-An Interesting Producer of Bioactive Plant Polyphenolic Metabolites.

Publications

<i>Saccharomyces Cerevisiae</i>-An Interesting Producer of Bioactive Plant Polyphenolic Metabolites.

Similar Datasets

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