scholarly journals Metabolic engineering of Saccharomyces cerevisiae for enhanced production of caffeic acid

Author(s):  
Pingping Zhou ◽  
Chunlei Yue ◽  
Bin Shen ◽  
Yi Du ◽  
Nannan Xu ◽  
...  
2020 ◽  
Author(s):  
Pingping Zhou ◽  
Chunlei Yue ◽  
Bin Shen ◽  
Yi Du ◽  
Nannan Xu ◽  
...  

Abstract 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.


2020 ◽  
Vol 7 (4) ◽  
pp. 135
Author(s):  
Jan Niklas Bröker ◽  
Boje Müller ◽  
Dirk Prüfer ◽  
Christian Schulze Gronover

Farnesyl diphosphate (FPP)-derived isoprenoids represent a diverse group of plant secondary metabolites with great economic potential. To enable their efficient production in the heterologous host Saccharomyces cerevisiae, we refined a metabolic engineering strategy using the CRISPR/Cas9 system with the aim of increasing the availability of FPP for downstream reactions. The strategy included the overexpression of mevalonate pathway (MVA) genes, the redirection of metabolic flux towards desired product formation and the knockout of genes responsible for competitive reactions. Following the optimisation of culture conditions, the availability of the improved FPP biosynthesis for downstream reactions was demonstrated by the expression of a germacrene synthase from dandelion. Subsequently, biosynthesis of significant amounts of germacrene-A was observed in the most productive strain compared to the wild type. Thus, the presented strategy is an excellent tool to increase FPP-derived isoprenoid biosynthesis in yeast.


Author(s):  
Wenqi Shi ◽  
Jie Li ◽  
Yanfang Chen ◽  
Xiaohang Liu ◽  
Yefu Chen ◽  
...  

2021 ◽  
Vol 69 (10) ◽  
pp. 3103-3113
Author(s):  
Junhua Wang ◽  
Wei Jiang ◽  
Chaojuan Liang ◽  
Linghuan Zhu ◽  
Youran Li ◽  
...  

2017 ◽  
Vol 27 (2) ◽  
pp. 81-90 ◽  
Author(s):  
Jolanta Mierzejewska ◽  
Aleksandra Tymoszewska ◽  
Karolina Chreptowicz ◽  
Kamil Krol

2-Phenylethanol (2-PE) is an aromatic alcohol with a rosy scent which is widely used in the food, fragrance, and cosmetic industries. Promising sources of natural 2-PE are microorganisms, especially yeasts, which can produce 2-PE by biosynthesis and biotransformation. Thus, the first challenging goal in the development of biotechnological production of 2-PE is searching for highly productive yeast strains. In the present work, 5 laboratory <i>Saccharomyces cerevisiae</i> strains were tested for the production of 2-PE. Thereafter, 2 of them were hybridized by a mating procedure and, as a result, a new diploid, <i>S. cerevisiae</i> AM1-d, was selected. Within the 72-h batch culture in a medium containing 5 g/L of <smlcap>L</smlcap>-phenylalanine, AM1-d produced 3.83 g/L of 2-PE in a shaking flask. In this way, we managed to select the diploid <i>S. cerevisiae</i> AM1-d strain, showing a 3- and 5-fold increase in 2-PE production in comparison to parental strains. Remarkably, the enhanced production of 2-PE by the hybrid of 2 yeast laboratory strains is demonstrated here for the first time.


2019 ◽  
Vol 21 (7) ◽  
pp. 1795-1808 ◽  
Author(s):  
Gregory Guirimand ◽  
Kentaro Inokuma ◽  
Takahiro Bamba ◽  
Mami Matsuda ◽  
Kenta Morita ◽  
...  

Xylitol is a major commodity chemical widely used in both the food and pharmaceutical industries.


Engineering ◽  
2019 ◽  
Vol 5 (2) ◽  
pp. 287-295 ◽  
Author(s):  
Lanqing Liu ◽  
Hong Liu ◽  
Wei Zhang ◽  
Mingdong Yao ◽  
Bingzhi Li ◽  
...  

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