Triggering the stringent response enhances synthetic methanol utilization in Escherichia coli
| Autor: | Jie Ren Gerald Har, Bryan von Hagel, Alec Agee, Ka-Hei Siu, Eleftherios T. Papoutsakis, Maciek R. Antoniewicz, R. Kyle Bennett |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
Stringent response Sigma Factor Bioengineering medicine.disease_cause 01 natural sciences Applied Microbiology and Biotechnology 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins Biosynthesis 010608 biotechnology Escherichia coli medicine Bioprocess Overproduction Amino acid synthesis 030304 developmental biology chemistry.chemical_classification 0303 health sciences Escherichia coli Proteins Methanol Gene Expression Regulation Bacterial Amino acid chemistry Biochemistry rpoS Biotechnology |
| Zdroj: | Metabolic Engineering. 61:1-10 |
| ISSN: | 1096-7176 |
| Popis: | Synthetic methylotrophy aims to engineer methane and methanol utilization pathways in platform hosts like Escherichia coli for industrial bioprocessing of natural gas and biogas. While recent attempts to engineer synthetic methylotrophs have proved successful, autonomous methylotrophy, i.e. the ability to utilize methane or methanol as sole carbon and energy substrates, has not yet been realized. Here, we address an important limitation of autonomous methylotrophy in E. coli: the inability of the organism to synthesize several amino acids when grown on methanol. By activating the stringent/stress response via ppGpp overproduction, or DksA and RpoS overexpression, we demonstrate improved biosynthesis of proteinogenic amino acids via endogenous upregulation of amino acid synthesis pathway genes. Thus, we were able to achieve biosynthesis of several limiting amino acids from methanol-derived carbon, in contrast to the control methylotrophic E. coli strain. This study addresses a key limitation currently preventing autonomous methylotrophy in E. coli and possibly other synthetic methylotrophs and provides insight as to how this limitation can be alleviated via stringent/stress response activation. |
| Databáze: | OpenAIRE |
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