In a groundbreaking development, researchers have engineered a highly efficient biosensor in yeast that could revolutionize the production of valuable natural products, with significant implications for the energy sector. The study, led by Xueqing Pang from the College of Bioscience and Biotechnology at Yangzhou University in China, was recently published in the journal *Synthetic Biology and Systems Biotechnology*.
The biosensor, developed in the yeast Saccharomyces cerevisiae, is designed to respond to p-coumaric acid, a crucial precursor in the biosynthesis of polyphenols and flavonoids. These compounds are not only valuable in the food and pharmaceutical industries but also hold promise for the production of biofuels and other energy-related applications.
The team constructed the biosensor by expressing the BsPadR repressor from Bacillus subtilis and engineering hybrid promoters. Notably, the PBS1-CCW12 hybrid promoter exhibited tight regulation by BsPadR and enhanced activity in response to p-coumaric acid. “This biosensor allows us to monitor and regulate intracellular biosynthesis pathways with unprecedented precision,” Pang explained. “It’s a significant step forward in our ability to optimize the production of natural products in microbial cell factories.”
However, the researchers encountered a challenge: excessive expression of BsPadR negatively impacted yeast growth. To mitigate this issue, they employed weaker promoters, PBST1 and PERG9. Additionally, they found that fusing an SV40-NLS (nuclear localization signal) at the C-terminus of BsPadR enhanced the biosensor’s performance.
To validate the biosensor’s utility, the team applied it to dynamically regulate CrtE, a key enzyme in lycopene biosynthesis. By coupling p-coumaric acid production with lycopene biosynthesis, they enabled high-throughput colorimetric screening for enzyme evolution and strain selection. This innovation could streamline the development of microbial strains optimized for the production of biofuels and other energy-related compounds.
The implications of this research extend beyond the laboratory. As the world seeks sustainable alternatives to fossil fuels, the ability to efficiently produce biofuels and other valuable compounds from microbial cell factories becomes increasingly important. “This biosensor is a powerful tool for future studies aimed at optimizing the production of p-coumaric acid and its derivatives,” Pang said. “It has the potential to significantly advance the efficiency of biosynthetic processes in microbial cell factories, benefiting not only the energy sector but also the food and pharmaceutical industries.”
The study represents a significant advancement in the field of synthetic biology, offering a novel approach to monitoring and regulating intracellular biosynthesis pathways. As researchers continue to refine and expand upon this technology, it could pave the way for more efficient and sustainable production of a wide range of valuable compounds, ultimately contributing to a more sustainable future.