{"id":"doi:10.1016/j.ymben.2017.10.011","kind":"review","title":"Design and application of genetically-encoded malonyl-CoA biosensors for metabolic engineering of microbial cell factories","authors":["Abayomi Oluwanbe Johnson","Miriam González‐Villanueva","Lynn Wong","Alexander Steinbüchel","Kang Lan Tee","Peng Xu","Tuck Seng Wong"],"author_count":7,"year":2017,"published":"2017-10-31","venue":"Metabolic Engineering","cited_by":122,"doi":"10.1016/j.ymben.2017.10.011","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.ymben.2017.10.011","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.ymben.2017.10.011","updated":null,"pmid":"29097310","pmcid":null,"openalex_id":"W2765868087","pdf_url":null,"abstract":"Malonyl-CoA is the basic building block for synthesizing a range of important compounds including fatty acids, phenylpropanoids, flavonoids and non-ribosomal polyketides. Centering around malonyl-CoA, we summarized here the various metabolic engineering strategies employed recently to regulate and control malonyl-CoA metabolism and improve cellular productivity. Effective metabolic engineering of microorganisms requires the introduction of heterologous pathways and dynamically rerouting metabolic flux towards products of interest. Transcriptional factor-based biosensors translate an internal cellular signal to a transcriptional output and drive the expression of the designed genetic/biomolecular circuits to compensate the activity loss of the engineered biosystem. Recent development of genetically-encoded malonyl-CoA sensor has stood out as a classical example to dynamically reprogram cell metabolism for various biotechnological applications. Here, we reviewed the design principles of constructing a transcriptional factor-based malonyl-CoA sensor with superior detection limit, high sensitivity and broad dynamic range. We discussed various synthetic biology strategies to remove pathway bottleneck and how genetically-encoded metabolite sensor could be deployed to improve pathway efficiency. Particularly, we emphasized that integration of malonyl-CoA sensing capability with biocatalytic function would be critical to engineer efficient microbial cell factory. Biosensors have also advanced beyond its classical function of a sensor actuator for in situ monitoring of intracellular metabolite concentration. Applications of malonyl-CoA biosensors as a sensor-invertor for negative feedback regulation of metabolic flux, a metabolic switch for oscillatory balancing of malonyl-CoA sink pathway and source pathway and a screening tool for engineering more efficient biocatalyst are also presented in this review. We envision the genetically-encoded malonyl-CoA sensor will be an indispensable tool to optimize cell metabolism and cost-competitively manufacture malonyl-CoA-derived compounds.","abstract_license":"CC-BY (publisher license, via OpenAlex)","license":"cc-by","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":["Microbial Metabolic Engineering and Bioproduction"],"details":null,"provenance":"openalex","attribution":"Abstract of \"Design and application of genetically-encoded malonyl-CoA biosensors for metabolic engineering of microbial cell factories\" by Abayomi Oluwanbe Johnson, Miriam González‐Villanueva, Lynn Wong et al., https://doi.org/10.1016/j.ymben.2017.10.011, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"synthetic-biology","name":"Synthetic Biology & Genome Engineering","domain_slug":"biotech"}],"cited_in_dossiers":[]}