Application of Metabolite-Responsive Biosensors for Plant Natural Products Biosynthesis

Abstract

Plant natural products (PNPs) have shown various pharmaceutical activities, possessing great potential in global markets. Microbial cell factories (MCFs) provide an economical and sustainable alternative for the synthesis of valuable PNPs compared with traditional approaches. However, the heterologous synthetic pathways always lack native regulatory systems, bringing extra burden to PNPs production. To overcome the challenges, biosensors have been exploited and engineered as powerful tools for establishing artificial regulatory networks to control enzyme expression in response to environments. Here, we reviewed the recent progress involved in the application of biosensors that are responsive to PNPs and their precursors. Specifically, the key roles these biosensors played in PNP synthesis pathways, including isoprenoids, flavonoids, stilbenoids and alkaloids, were discussed in detail.

Genetically encoded Boolean logic operators to sense and integrate phenylpropanoid metabolite levels in plants

“…Among these, aTFs like TtgR, CouR, PadR, FdeR and FerC are responsive to phenylpropanoid-related molecules (Ferreira & Antunes 2021), making them good sensor candidates to engineer plants with the goal of manipulating the synthesis of phenylpropanoid-derived metabolites. In fact, several of these sensors have been deployed in microbial systems to engineer phenylpropanoid producing strains (Zhang et al, 2023). These aTFs can sense the metabolic status of the microbial cell, thereby providing dynamic regulation of an introduced pathway based on metabolite levels.…”

Genetically encoded Boolean logic operators to sense and integrate phenylpropanoid metabolite levels in plants

“…Among these, TtgR (Fernandez‐Escamilla et al ., 2015), CouR (Hirakawa et al ., 2012), PadR (Tran et al ., 2008), FdeR (Marin et al ., 2013), and FerC (Kasai et al ., 2012) are responsive to phenylpropanoid‐related molecules, making them good sensor candidates to engineer plants with the goal of manipulating the synthesis of phenylpropanoid‐derived metabolites. In fact, several of these sensors have been deployed in microbial systems to engineer phenylpropanoid‐producing strains (Zhang et al ., 2023). These aTFs can sense the metabolic status of the microbial cell, thereby providing dynamic regulation of an introduced pathway based on metabolite levels.…”

Investigating and Engineering an 1,2-Propanediol-Responsive Transcription Factor-Based Biosensor

“…Metabolic engineering strategically manipulates and reconstructs metabolic pathways in microbes to environmentally and sustainably produce a diverse array of compounds vital for industrial applications, such as fuels and pharmaceuticals. , Despite significant advancements, there are still challenges in achieving optimal titers, yields, and productivities, including the difficulty to obtain effective genes and enzymes, as well as the imbalances and burdens brought by heterologous gene expression. − Over the years, transcription factor (TF)-based biosensors have been playing a pivotal role in addressing these challenges. − These biosensors can modulate gene expression in response to specific biomolecule signals. With fluorescence as output, TF-based biosensors have enabled the high-throughput screening of various overproducers for the biosynthesis of lactam, l -cysteine, p -coumaric acid, and butanol .…”

“… 3 − 5 Over the years, transcription factor (TF)-based biosensors have been playing a pivotal role in addressing these challenges. 6 − 8 These biosensors can modulate gene expression in response to specific biomolecule signals. With fluorescence as output, TF-based biosensors have enabled the high-throughput screening of various overproducers for the biosynthesis of lactam, 9 l -cysteine, 10 p -coumaric acid, 11 and butanol.…”