Yeast Synthetic Biology Approaches for the Production of Valuable Polyphenolic Compounds

Gomes, Daniela; Rainha, João; Rodrigues, L. R.; Rodrigues, Joana Lúcia Lima Correia

doi:10.1007/978-3-030-89680-5_5

Cited by 6 publications

(5 citation statements)

References 123 publications

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“…Although E. coli has been considered an alternative chassis to produce several plant secondary metabolites, other hosts might be more suitable to engineer the furanocoumarins pathway. The S. cerevisiae genetic toolbox is also highly developed [ 76 ] and, as an eukaryote, it can perform post-translational modifications and contains intracellular compartments similar to plants [ 22 , 77 ]. This makes it a more suitable host for the expression of plant enzymes, including CYP450.…”

Section: Discussionmentioning

confidence: 99%

Challenges in the Heterologous Production of Furanocoumarins in Escherichia coli

2022

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Coumarins and furanocoumarins are plant secondary metabolites with known biological activities. As they are present in low amounts in plants, their heterologous production emerged as a more sustainable and efficient approach to plant extraction. Although coumarins biosynthesis has been positively established, furanocoumarin biosynthesis has been far more challenging. This study aims to evaluate if Escherichia coli could be a suitable host for furanocoumarin biosynthesis. The biosynthetic pathway for coumarins biosynthesis in E. coli was effectively constructed, leading to the production of umbelliferone, esculetin and scopoletin (128.7, 17.6, and 15.7 µM, respectively, from tyrosine). However, it was not possible to complete the pathway with the enzymes that ultimately lead to furanocoumarins production. Prenyltransferase, psoralen synthase, and marmesin synthase did not show any activity when expressed in E. coli. Several strategies were tested to improve the enzymes solubility and activity with no success, including removing potential N-terminal transit peptides and expression of cytochrome P450 reductases, chaperones and/or enzymes to increase dimethylallylpyrophosphate availability. Considering the results herein obtained, E. coli does not seem to be an appropriate host to express these enzymes. However, new alternative microbial enzymes may be a suitable option for reconstituting the furanocoumarins pathway in E. coli. Nevertheless, until further microbial enzymes are identified, Saccharomyces cerevisiae may be considered a preferred host as it has already been proven to successfully express some of these plant enzymes.

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Section: Discussionmentioning

confidence: 99%

Challenges in the Heterologous Production of Furanocoumarins in Escherichia coli

2022

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“…Advances on metabolic engineering have allowed researchers to develop genetically modified microorganisms able to produce plant-derived compounds such as flavonoids, stilbenes, or curcuminoids (Rodrigues et al 2015b;Rainha et al 2020;Gomes et al 2021). E. coli is the most notorious biological chassis for this kind of application, because it is easy to manipulate and to handle.…”

Section: Metabolic Engineering Of E Coli To Produce Curcuminoidsmentioning

confidence: 99%

Microbial Production of Curcumin

Rainha

Rodrigues

2022

Microbial Production of Food Bioactive Compounds

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Curcumin, a polyphenol produced by turmeric (Curcuma longa), has attracted increased attention due to its potential as a novel cancer-fighting drug. However, to satisfy the required curcumin demand for health-related studies, high purity curcumin preparations are required, which are difficult to obtain and are very expensive. Curcumin and other curcuminoids are usually obtained through plant extraction. However, these polyphenols accumulate in low amounts over long

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“…The extensive molecular tools available, such as the Clustered Regularly Interspaced Palindromic Repeats (CRISPR)-Cas9 based ones, allow the genomic integration of multiple heterologous genes without requiring antibiotic markers . Furthermore, significant research has been dedicated to the biosynthesis of plant polyphenols in this yeast. , Curcumin biosynthesis, in C. longa, is accomplished by reactions catalyzed by the type III polyketide synthases (PKSs), diketide-CoA synthase (DCS), and curcumin synthase (CURS).…”

Section: Introductionmentioning

confidence: 99%

“… 22 Furthermore, significant research has been dedicated to the biosynthesis of plant polyphenols in this yeast. 23 , 24 Curcumin biosynthesis, in C. longa , is accomplished by reactions catalyzed by the type III polyketide synthases (PKSs), diketide-CoA synthase (DCS), and curcumin synthase (CURS). Three isoforms of CURS were identified in C. longa , each one with a different substrate affinity explaining the diversity of curcuminoids found in turmeric.…”

Section: Introductionmentioning

confidence: 99%

De Novo Biosynthesis of Curcumin in Saccharomyces cerevisiae

Rainha,

Rodrigues,

Rodrigues

2024

ACS Synth. Biol.

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Curcumin, a natural polyphenol derived from turmeric, has attracted immense interest due to its diverse pharmacological properties. Traditional extraction methods from Curcuma longa plants present limitations in meeting the growing demand for this bioactive compound, giving significance to its production by genetically modified microorganisms. Herein, we have developed an engineered Saccharomyces cerevisiae to produce curcumin from glucose. A pathway composed of the 4-hydroxyphenylacetate 3-monooxygenase oxygenase complex from Pseudomonas aeruginosa and Salmonella enterica, caffeic acid O-methyltransferase from Arabidopsis thaliana, feruloyl-CoA synthetase from Pseudomonas paucimobilis, and diketide-CoA synthase and curcumin synthase from C. longa was introduced in a p-coumaric acid overproducing S. cerevisiae strain. This strain produced 240.1 ± 15.1 μg/L of curcumin. Following optimization of phenylpropanoids conversion, a strain capable of producing 4.2 ± 0.6 mg/L was obtained. This study reports for the first time the successful de novo production of curcumin in S. cerevisiae.

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Yeast Synthetic Biology Approaches for the Production of Valuable Polyphenolic Compounds

Cited by 6 publications

References 123 publications

Challenges in the Heterologous Production of Furanocoumarins in Escherichia coli

Challenges in the Heterologous Production of Furanocoumarins in Escherichia coli

Microbial Production of Curcumin

De Novo Biosynthesis of Curcumin in Saccharomyces cerevisiae

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