In a groundbreaking development for the bioproduction of high-value compounds, researchers have successfully engineered the oleaginous yeast Yarrowia lipolytica to co-produce thymol and carvacrol, two phenolic monoterpenes with extensive applications in the spice and medicine industries. This achievement, led by Junkai Zhu from the Key Laboratory of Marine Biotechnology of Zhejiang Province at Ningbo University, marks the first de novo synthesis of these compounds in Y. lipolytica, opening new avenues for sustainable and scalable production.
Thymol and carvacrol are natural phenolic compounds renowned for their antimicrobial, antioxidant, and anti-inflammatory properties. Traditionally, these compounds are extracted from plants of the Thymus genus or the Lamiaceae family, a process that is often labor-intensive and subject to environmental fluctuations. The ability to produce these compounds via microbial cell factories not only offers a more consistent and controllable alternative but also aligns with the growing demand for sustainable and eco-friendly production methods.
The research team’s approach involved constructing the complete synthetic pathways of thymol and carvacrol in Y. lipolytica. By enhancing the mevalonate pathway and reducing the metabolic flux from geranyl diphosphate (GPP) to farnesyl diphosphate (FPP) through modifications of the ERG20 gene, they achieved a significant 18.44-fold increase in the total titer of thymol and carvacrol. Further optimization, including increasing the copy number of the TvCYP71D507 gene combination, led to an additional 1.75-fold increase in titer.
“Our goal was to create a robust and efficient microbial system for the production of these valuable compounds,” said Junkai Zhu, the lead author of the study. “By leveraging the metabolic capabilities of Y. lipolytica, we were able to achieve a substantial increase in production, demonstrating the potential of synthetic biology in addressing industrial demands.”
The engineered strain, CT18, which was reintroduced with the 3-isopropylmalate dehydrogenase (LEU2) gene, achieved a titer of 7.14 mg/L in shake flasks and an impressive 61.31 mg/L in a 5-L bioreactor. These results not only highlight the efficacy of the engineered pathways but also pave the way for further optimization and scale-up in industrial settings.
The implications of this research extend beyond the immediate production of thymol and carvacrol. The successful engineering of Y. lipolytica for the biosynthesis of phenolic monoterpenes sets a precedent for the development of microbial cell factories for other high-value compounds. This could revolutionize the bioproduction industry, offering more sustainable and cost-effective solutions for the production of a wide range of natural products.
As the demand for natural and sustainable products continues to grow, the ability to produce high-value compounds through microbial cell factories becomes increasingly important. This research not only provides a valuable reference for constructing microbial cell factories for phenolic monoterpenes biosynthesis but also underscores the potential of synthetic biology in shaping the future of the bioproduction industry.
Published in the journal ‘Microbial Cell Factories’ (translated to English as ‘微生物细胞工厂’), this study represents a significant step forward in the field of synthetic biology and bioproduction. The findings offer a promising glimpse into the future of sustainable and scalable production of high-value compounds, with far-reaching implications for the energy and biotechnology sectors.