Promoter-Library-Based Pathway Optimization for Efficient (2S)-Naringenin Production from p-Coumaric Acid in Saccharomyces cerevisiae

2020 ◽  
Vol 68 (25) ◽  
pp. 6884-6891 ◽  
Author(s):  
Song Gao ◽  
Hengrui Zhou ◽  
Jingwen Zhou ◽  
Jian Chen
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Coumaric Acid ◽  
Pathway Optimization ◽  
Promoter Library

Efficient Biosynthesis of (2S)-Naringenin from p-Coumaric Acid in Saccharomyces cerevisiae

2019 ◽  
Vol 68 (4) ◽  
pp. 1015-1021 ◽  
Author(s):  
Song Gao ◽  
Yunbin Lyu ◽  
Weizhu Zeng ◽  
Guocheng Du ◽  
Jingwen Zhou ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Coumaric Acid

scholarly journals Metabolic engineering and transcriptomic analysis of Saccharomyces cerevisiae producing p-coumaric acid from xylose

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Gheorghe M. Borja ◽  
Angelica Rodriguez ◽  
Kate Campbell ◽  
Irina Borodina ◽  
Yun Chen ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Metabolic Engineering ◽  
Carbon Source ◽  
Aromatic Amino Acids ◽  
Transcriptomic Analysis ◽  
Scale Production ◽  
Coumaric Acid ◽  
Future Production ◽  
Glyoxylate Pathway ◽  
Industrial Scale Production

Abstract Background Aromatic amino acids and their derivatives are valuable chemicals and are precursors for different industrially compounds. p-Coumaric acid is the main building block for complex secondary metabolites in commercial demand, such as flavonoids and polyphenols. Industrial scale production of this compound from yeast however remains challenging. Results Using metabolic engineering and a systems biology approach, we developed a Saccharomyces cerevisiae platform strain able to produce 242 mg/L of p-coumaric acid from xylose. The same strain produced only 5.35 mg/L when cultivated with glucose as carbon source. To characterise this platform strain further, transcriptomic analysis was performed, comparing this strain’s growth on xylose and glucose, revealing a strong up-regulation of the glyoxylate pathway alongside increased cell wall biosynthesis and unexpectedly a decrease in aromatic amino acid gene expression when xylose was used as carbon source. Conclusions The resulting S. cerevisiae strain represents a promising platform host for future production of p-coumaric using xylose as a carbon source.

scholarly journals Highly Active and Specific Tyrosine Ammonia-Lyases from Diverse Origins Enable Enhanced Production of Aromatic Compounds in Bacteria and Saccharomyces cerevisiae

2015 ◽  
Vol 81 (13) ◽  
pp. 4458-4476 ◽  
Author(s):  
Christian Bille Jendresen ◽  
Steen Gustav Stahlhut ◽  
Mingji Li ◽  
Paula Gaspar ◽  
Solvej Siedler ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Saccharomyces Cerevisiae ◽  
Cinnamic Acid ◽  
Aromatic Compounds ◽  
Physcomitrella Patens ◽  
Coumaric Acid ◽  
Content Type ◽  
Highly Active ◽  
Enhanced Production ◽  
Wide Range

ABSTRACTPhenylalanine and tyrosine ammonia-lyases form cinnamic acid andp-coumaric acid, which are precursors of a wide range of aromatic compounds of biotechnological interest. Lack of highly active and specific tyrosine ammonia-lyases has previously been a limitation in metabolic engineering approaches. We therefore identified 22 sequencesin silicousing synteny information and aiming for sequence divergence. We performed a comparativein vivostudy, expressing the genes intracellularly in bacteria and yeast. When produced heterologously, some enzymes resulted in significantly higher production ofp-coumaric acid in several different industrially important production organisms. Three novel enzymes were found to have activity exclusively for phenylalanine, including an enzyme from the low-GC Gram-positive bacteriumBrevibacillus laterosporus, a bacterial-type enzyme from the amoebaDictyostelium discoideum, and a phenylalanine ammonia-lyase from the mossPhyscomitrella patens(producing 230 μM cinnamic acid per unit of optical density at 600 nm [OD600]) in the medium usingEscherichia colias the heterologous host). Novel tyrosine ammonia-lyases having higher reported substrate specificity than previously characterized enzymes were also identified. Enzymes fromHerpetosiphon aurantiacusandFlavobacterium johnsoniaeresulted in high production ofp-coumaric acid inEscherichia coli(producing 440 μMp-coumaric acid OD600unit−1in the medium) and inLactococcus lactis. The enzymes were also efficient inSaccharomyces cerevisiae, wherep-coumaric acid accumulation was improved 5-fold over that in strains expressing previously characterized tyrosine ammonia-lyases.

Combinatorial analysis of enzymatic bottlenecks of l-tyrosine pathway by p-coumaric acid production in Saccharomyces cerevisiae

2017 ◽  
Vol 39 (7) ◽  
pp. 977-982 ◽  
Author(s):  
Jiwei Mao ◽  
Quanli Liu ◽  
Xiaofei Song ◽  
Hesuiyuan Wang ◽  
Hui Feng ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Acid Production ◽  
Combinatorial Analysis ◽  
Coumaric Acid

scholarly journals Comparative Activity of Six Recombinant Stilbene Synthases in Yeast for Resveratrol Production

2020 ◽  
Vol 10 (14) ◽  
pp. 4847
Author(s):  
Nemesio Villa-Ruano ◽  
Antonio Rivera ◽  
Efraín Rubio-Rosas ◽  
Gerardo Landeta-Cortés ◽  
Jenaro Leocadio Varela-Caselis ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Batch Fermentation ◽  
Expression Vector ◽  
The Other ◽  
Acidic Ph ◽  
Polygonum Cuspidatum ◽  
Recombinant Yeast ◽  
Coumaric Acid ◽  
Comparative Activity

Resveratrol is a nutraceutical with relevant benefits to human health. This investigation reports on the generation and evaluation of six recombinant yeast lines that produce resveratrol from p-coumaric acid. The yeast lines contained a single p-coumaric acid-Co-A ligase from Plagiochasma appendiculatum combined with the stilbene synthases from Parthenocissus henryana, Polygonum cuspidatum, Morus alba var. atropurpurea, Rheum tataricum, Vitis vinifera and Arachis hypogaea. Codon optimized versions of these sequences were inserted in an expression vector flanked by the constitutive PGK and GPD promoters before expression in Saccharomyces cerevisiae. Batch fermentation (60 h) revealed that yeast lines had different capacities (p < 0.01) to produce resveratrol. Slightly acidic pH (6) and concentrations <100 mg L−1 p-coumaric acid improved resveratrol yields. Among the six lines, those containing the stilbene synthases (STS) from P. cuspidatum and M. alba produced up to 39 mg L−1 using 70 mg L−1 p-coumaric acid. On the other hand, lines expressing STS from V. vinifera, A. hypogaea and R. tataricum generated resveratrol faster than other lines but accumulated lower amounts at the end of the batch period (27–30 mg L−1). The simultaneous consumption of ethanol and p-coumaric acid corroborates the role of ethanol as a carbon source involved in the conversion of p-coumaric acid into resveratrol.

scholarly journals Production of Resveratrol in Recombinant Microorganisms

2006 ◽  
Vol 72 (8) ◽  
pp. 5670-5672 ◽  
Author(s):  
Jules Beekwilder ◽  
Rianne Wolswinkel ◽  
Harry Jonker ◽  
Robert Hall ◽  
C. H. Ric de Vos ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Saccharomyces Cerevisiae ◽  
Culture Medium ◽  
Stilbene Synthase ◽  
Coumaric Acid ◽  
E Coli ◽  
Recombinant Microorganisms

ABSTRACT Resveratrol production in Saccharomyces cerevisiae was compared to that in Escherichia coli. In both systems, 4-coumarate:coenzyme A ligase from tobacco and stilbene synthase from grapes were expressed. When p-coumaric acid was used as the precursor, resveratrol accumulations in the culture medium were observed to be comparable in E. coli (16 mg/liter) and yeast (6 mg/liter).

scholarly journals Optimization of the l-tyrosine metabolic pathway in Saccharomyces cerevisiae by analyzing p-coumaric acid production

3 Biotech ◽  
2020 ◽  
Vol 10 (6) ◽  
Author(s):  
Yuanzi Li ◽  
Jiwei Mao ◽  
Xiaofei Song ◽  
Yuzhen Wu ◽  
Miao Cai ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Metabolic Pathway ◽  
Acid Production ◽  
Coumaric Acid

scholarly journals Recombinant Saccharomyces cerevisiae Strain Expressing a Model Cytochrome P450 in the Rat Digestive Environment: Viability and Bioconversion Activity

2007 ◽  
Vol 73 (11) ◽  
pp. 3566-3574 ◽  
Author(s):  
G. Garrait ◽  
J. F. Jarrige ◽  
S. Blanquet ◽  
E. Beyssac ◽  
M. Alric
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Drug Delivery ◽  
Oral Administration ◽  
Digestive Tract ◽  
Drug Delivery Systems ◽  
Recombinant Yeast ◽  
Coumaric Acid ◽  
Recombinant Microorganisms ◽  
Small Intestinal

ABSTRACT An innovative “biodrug” concept, based on the oral administration of living recombinant microorganisms, has recently emerged for the prevention or treatment of various diseases. An engineered Saccharomyces cerevisiae strain expressing plant P450 73A1 (cinnamate-4-hydroxylase [CA4H] activity) was used, and its survival and ability to convert trans-cinnamic acid (CIN) into p-coumaric acid (COU) were investigated in vivo. In rats, the recombinant yeast was resistant to gastric and small intestinal secretions but was more sensitive to the conditions found in the large intestine. After oral administration of yeast and CIN, the CA4H activity was shown in vivo, with COU being found throughout the rat's digestive tract and in its urine. The bioconversion reaction occurred very fast, with most of the COU being produced within the first 5 min. The gastrointestinal sac technique demonstrated that the recombinant yeast was able to convert CIN into COU (conversion rate ranging from 2 to 5%) in all the organs of the rat's digestive tract: stomach, duodenum, jejunum, ileum, cecum, and colon. These results promise new opportunities for the development of drug delivery systems based on engineered yeasts catalyzing a bioconversion reaction directly in the digestive tract.

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