Yeast Metabolic Engineering for Biosynthesis of Caffeic Acid-Derived Phenethyl Ester and Phenethyl Amide.
Zi-Chen JiaDuo LiuHai-Di MaYu-Hui CuiHui-Min LiXia LiYing-Jin YuanPublished in: ACS synthetic biology (2023)
Caffeic acid (CA)-derived phenethyl ester (CAPE) and phenethyl amide (CAPA) are extensively investigated bioactive compounds with therapeutic applications such as antioxidant, anti-inflammatory, and anticarcinogenic properties. To construct microbial cell factories for production of CAPE or CAPA is a promising option given the limitation of natural sources for product extraction and the environmental toxicity of the agents used in chemical synthesis. We reported the successful biosynthesis of caffeic acid in yeast previously. Here in this work, we further constructed the downstream synthetic pathways in yeast for biosynthesis of CAPE and CAPA. After combinatorial engineering of yeast chassis based on the rational pathway engineering method and library-based SCRaMbLE method, we finally obtained the optimal strains that respectively produced 417 μg/L CAPE and 1081 μg/L CAPA. Two screened gene targets of ΔHAM1 and ΔYJL028W were discovered to help improve the product synthesis capacity. This is the first report of the de novo synthesis of CAPA from glucose in an engineered yeast chassis. Future work on enzyme and chassis engineering will further support improving the microbial cell factories for the production of CA derivatives.
Keyphrases
- cell wall
- south africa
- saccharomyces cerevisiae
- anti inflammatory
- single cell
- microbial community
- oxidative stress
- cell therapy
- multidrug resistant
- escherichia coli
- stem cells
- type diabetes
- wastewater treatment
- metabolic syndrome
- blood pressure
- gene expression
- genome wide
- drinking water
- risk assessment
- mass spectrometry
- blood glucose
- dna methylation
- adipose tissue
- human health
- weight loss
- high speed