Engineering the Biosynthesis of Caffeic Acid in Saccharomyces cerevisiae with Heterologous Enzyme Combinations

Liu, Lanqing; Liu, Hong; Zhang, Wei; Yao, Minyu; Li, Bingzhi; Liu, Duo; Yuan, Ying‐Jin

doi:10.1016/j.eng.2018.11.029

Cited by 54 publications

(51 citation statements)

References 42 publications

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“…The extension of this pathway leads to the production of caffeic acid and ferulic acid [ 209 ]. The conversion of coumaric acid to caffeic acid can be mediated by 4-hydroxyphenylacetate 3-hydroxylase ( 4hp3h ), 4-coumarate 3-hydroxylase encoded in sam5 , 4-hydroxyphenylacetate 3-monooxygenase ( hpaC and hpaB ), or cytochrome P450 [ 210 , 211 , 212 , 213 , 214 ]. Therefore, for the latter, it is difficult to express in the bacterial systems and requires the co-expression of redox partners—the putida redoxin reductase gene ( pdR ) and the palustris redoxin gene ( pux ) from Rhodopseudomonas palustris in the host organism [ 210 , 215 ].…”

Section: Production Of Phenolic Acids Using Non-modified and Enginmentioning

confidence: 99%

“…Some examples from literature [ 199 , 204 , 205 , 206 , 207 , 208 , 209 , 210 , 214 , 217 , 218 , 221 , 224 , 225 , 226 , 227 , 228 , 231 , 233 , 234 , 235 , 236 , 237 , 238 , 239 , 240 , 241 , 242 , 243 , 244 ] of the highest production of phenolic acids biosynthesised by the engineered microorganisms are presented in Supplementary Materials Table S1 . However, there are no data on the production of other phenolic acids, such as isovanillic, o -vanillic ( 7 ), and isoferulic acids and isomers of p -coumaric, 6-methyl salicylic, and α-resorcyllic acids, by the engineered microorganisms.…”

Section: Production Of Phenolic Acids Using Non-modified and Enginmentioning

confidence: 99%

“…Transposon mutagenesis and codon optimisation techniques were applied for vanillic, caffeic, and p -hydroxybenzoic acid production in engineered microorganisms [ 205 , 214 , 233 , 236 ]. For successful p -coumaric acid biosynthesis, researchers applied high-throughput sequencing technology and gene overexpression via the CRISPR /Cas9 system [ 207 , 208 ].…”

Section: Future Perspectives and Limitations Of Phenolic Acid Prodmentioning

confidence: 99%

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Advances and Prospects of Phenolic Acids Production, Biorefinery and Analysis

et al. 2020

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Biotechnological production of phenolic acids is attracting increased interest due to their superior antioxidant activity, as well as other antimicrobial, dietary, and health benefits. As secondary metabolites, primarily found in plants and fungi, they are effective free radical scavengers due to the phenolic group available in their structure. Therefore, phenolic acids are widely utilised by pharmaceutical, food, cosmetic, and chemical industries. A demand for phenolic acids is mostly satisfied by utilising chemically synthesised compounds, with only a low quantity obtained from natural sources. As an alternative to chemical synthesis, environmentally friendly bio-based technologies are necessary for development in large-scale production. One of the most promising sustainable technologies is the utilisation of microbial cell factories for biosynthesis of phenolic acids. In this paper, we perform a systematic comparison of the best known natural sources of phenolic acids. The advances and prospects in the development of microbial cell factories for biosynthesis of these bioactive compounds are discussed in more detail. A special consideration is given to the modern production methods and analytics of phenolic acids.

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Section: Production Of Phenolic Acids Using Non-modified and Enginmentioning

confidence: 99%

Section: Production Of Phenolic Acids Using Non-modified and Enginmentioning

confidence: 99%

Section: Future Perspectives and Limitations Of Phenolic Acid Prodmentioning

confidence: 99%

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Advances and Prospects of Phenolic Acids Production, Biorefinery and Analysis

et al. 2020

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“…Biosynthesis of caffeic acid could be derived from tyrosine, while S. cerevisiae cells do not possess the pathway downstream of tyrosine. For heterologous biosynthesis of caffeic acid, RgTAL ( KF765779.1) from R. glutinis, HpaB (PHSS01000001.1) from Pseudomonas aeruginosa and HpaC from S. enterica reported with excellent performance [11,31] were chosen as the target genes for pathway construction.…”

Section: Resultsmentioning

confidence: 99%

Metabolic engineering of Saccharomyces cerevisiae for enhanced production of caffeic acid

Zhou

Yue

Shen

et al. 2020

Preprint

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Background As a natural phenolic acid product of plant source, caffeic acid displays diverse biological activities and acts as an important precursor for the synthesis of other valuable compounds. Limitations in chemical synthesis or plant extraction of caffeic acid trigger interest in its microbial biosynthesis. Recently, Saccharomyces cerevisiae has been reported sporadically for biosynthesis of caffeic acid via free plasmid‑mediated pathway assembly. However, the production was far from satisfactory and even relied on the addition of precursor. Results In this study, we first established a controllable caffeic acid pathway by employing a modified GAL regulatory system in S. cerevisiae and realized de novo biosynthesis of 313.8 mg/L caffeic acid from glucose. Combinatorial engineering strategies including eliminating the tyrosine-induced feedback inhibition, deleting genes involved in competing pathways and overexpressing rate-limiting enzymes led to about 2.5-fold improvement in the caffeic acid production, reaching up to 769.3 mg/L in shake-flask cultures. To our knowledge, this is the highest ever reported titer of caffeic acid de novo synthesized by engineered yeast. Conclusions Caffeic acid production in S. cerevisiae strain was successfully improved by adopting a glucose-regulated GAL system and comprehensive metabolic engineering strategies. This work showed the prospect for microbial biosynthesis of caffeic acid and laid the foundation for constructing biosynthetic pathways of its derived metabolites.

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“…The overexpression of Rhodotorula glutinis tal and S. espanaensis 4coumarate 3-hydroxylase gene in a tyrosine-overproducing E. coli strain yielded 106 mg/L of caffeic acid in a 2-L bioreactor batch fermentation process (Zhang and Stephanopoulos, 2013). HpaB from Pseudomonas aeruginosa and HpaC from Salmonella enterica along with Tal from Rhodosporidium toruloides was overexpressed in S. cerevisiae for the production of caffeic acid, which reached 289.4 mg/L (Liu L. et al, 2019). This is the first report on engineering S. cerevisiae for the production of caffeic acid.…”

Section: S Cerevisiae S288cmentioning

confidence: 99%

Recent Advances in Metabolically Engineered Microorganisms for the Production of Aromatic Chemicals Derived From Aromatic Amino Acids

Shen

Niu

Yan

et al. 2020

Front. Bioeng. Biotechnol.

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Aromatic compounds derived from aromatic amino acids are an important class of diverse chemicals with a wide range of industrial and commercial applications. They are currently produced via petrochemical processes, which are not sustainable and eco-friendly. In the past decades, significant progress has been made in the construction of microbial cell factories capable of effectively converting renewable carbon sources into value-added aromatics. Here, we systematically and comprehensively review the recent advancements in metabolic engineering and synthetic biology in the microbial production of aromatic amino acid derivatives, stilbenes, and benzylisoquinoline alkaloids. The future outlook concerning the engineering of microbial cell factories for the production of aromatic compounds is also discussed.

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Engineering the Biosynthesis of Caffeic Acid in Saccharomyces cerevisiae with Heterologous Enzyme Combinations

Cited by 54 publications

References 42 publications

Advances and Prospects of Phenolic Acids Production, Biorefinery and Analysis

Advances and Prospects of Phenolic Acids Production, Biorefinery and Analysis

Metabolic engineering of Saccharomyces cerevisiae for enhanced production of caffeic acid

Recent Advances in Metabolically Engineered Microorganisms for the Production of Aromatic Chemicals Derived From Aromatic Amino Acids

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