Abstract
BackgroundMalonyl-coenzyme A (CoA) is an important biosynthetic precursor in vivo. Although Escherichia coli is a useful organism for biosynthetic applications, its malonyl-CoA level is too low.ResultsTo identify strains with the best potential for enhanced malonyl-CoA production, we developed a whole-cell biosensor for rapidly reporting intracellular malonyl-CoA concentrations. The biosensor was successfully applied as a high-throughput screening tool for identifying targets at a genome-wide scale that could be critical for improving the malonyl-CoA biosynthesis in vivo. The mutant strains selected synthesized significantly higher titers of the type III polyketide triacetic acid lactone (TAL), phloroglucinol, and free fatty acids compared to the wild-type strain, using malonyl-CoA as a precursor.ConclusionThese results validated this novel whole-cell biosensor as a rapid and sensitive malonyl-CoA high-throughput screening tool. Further analysis of the mutant strains showed that the iron ion concentration is closely related to the intracellular malonyl-CoA biosynthesis.
Highlights
Malonyl-coenzyme A (CoA) is an important biosynthetic precursor in vivo
The main carbon flow from pyruvate and acetyl-CoA flows into the tricarboxylic acid (TCA) cycle, and only a small portion transforms into malonyl-CoA which participates in fatty acid biosynthesis [10]
In the Design and validation of a whole‐cell biosensor of malonyl‐CoA To effectively monitor the malonyl-CoA biosynthesis in E. coli, a malonyl-CoA whole-cell biosensor was developed based on a mutated transcriptional regulatory protein AraC that is responsive to triacetic acid lactone (TAL) (AraC-TAL) [17]
Summary
Malonyl-coenzyme A (CoA) is an important biosynthetic precursor in vivo. Escherichia coli is a useful organism for biosynthetic applications, its malonyl-CoA level is too low. Malonyl-coenzyme (CoA) is an essential building block for the biosynthesis of natural products, including fatty acids, polyketides, stilbenes and flavonoids, by providing the two-carbon units. Many of these compounds show beneficial properties for medical applications, including anti-cancer, anti-bacterial, antiviral, anti-inflammatory and anti-allergic activities, as well as in the development of agricultural products (e.g., insecticides) [1,2,3,4,5]. E. coli has become a widely used host for the industrial production of chemicals and fuels given that its genetic background To this end, metabolic engineering strategies to elevate the intracellular malonyl-CoA biosynthesis in E. coli have been reported (Fig. 1).
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