Metabolic engineering of Escherichia coli for agmatine production

Abstract

Agmatine is a kind of important biogenic amine. The chemical synthesis route is not a desirable choice for industrial production of agmatine. To date, there are no reports on the fermentative production of agmatine by microorganism. In this study, the base Escherichia coli strain AUX4 (JM109 ∆speC ∆speF ∆speB ∆argR) capable of excreting agmatine into the culture medium was first constructed by sequential deletions of the speC and speF genes encoding the ornithine decarboxylase isoenzymes, the speB gene encoding agmatine ureohydrolase and the regulation gene argR responsible for the negative control of the arg regulon. The speA gene encoding arginine decarboxylase harboured by the pKK223‐3 plasmid was overexpressed in AUX4, resulting in the engineered strain AUX5. The batch and fed‐batch fermentations of the AUX5 strain were conducted in a 3‐L bioreactor, and the results showed that the AUX5 strain was able to produce 1.13 g agmatine L−1 with the yield of 0.11 g agmatine g−1 glucose in the batch fermentation and the fed‐batch fermentation of AUX5 allowed the production of 15.32 g agmatine L−1 with the productivity of 0.48 g agmatine L−1 h−1, demonstrating the potential of E. coli as an industrial producer of agmatine.

Pathway Engineering for Phenethylamine Production in Escherichia coli

“…Biogenic amines such as agmatine and spermidine are toxic to the producer cells if they accumulate at a high concentration. , For fermentative production of phenethylamine, it was necessary to perform a phenethylamine tolerance test in E. coli.…”

“…coli (Figure ). The increase in the NADPH supply contributed to improving interesting metabolite production. , The first reaction catalyzed by the zwf gene encoding glucose-6-phosphate dehydrogenase is the rate-limiting step in the PPP . In this study, the zwf gene was overexpressed by replacing the native promoters with the core- trc promoter, generating the final engineered E.…”

Improvement of putrescine production through the arginine decarboxylase pathway in Escherichia coli K-12

“…The biosynthetic pathway of arginine initiates with glutamate to N -acetylglutamate by N -acetylglutamate synthase (ArgA), which is encoded by argA . However, not only is the transcription of the argA gene repressed by ArgR, but the activity of ArgA is also inhibited by the final product arginine (Lu 2006 ; Sun et al 2015 ; Xu and Zhang 2019a , b ). To produce putrescine from glutamate, the repression of argA by ArgR and the feedback inhibition of ArgA by arginine are of concern.…”

High-level production of the agmatine in engineered Corynebacterium crenatum with the inhibition-releasing arginine decarboxylase

“…Currently, Escherichia coli is an attractive microbial chassis to produce various substances by metabolic engineering, since it has a clear genetic background [ 10 – 12 ]. Xu et al had constructed a series of engineered E. coli for agmatine production [ 13 , 14 ]. They first constructed an engineered E. coli for agmatine production through the deletion of speC and speF (encoding the ornithine decarboxylase isoenzymes), speB (encoding agmatinase) and argR (encoding a transcriptional repressor).…”

“…And then, the arginine decarboxylase gene speA from E. coli was overexpressed in the base strain AUX4, generating the strain AUX5. The engineered strain E. coli AUX5 produced 15.32 g/L agmatine with a yield of 0.11 g/g glucose in fed-batch fermentation [ 13 ]. Xu et al used heterologous strong promoters sequentially to overexpress the genes encoding glutamate dehydrogenase ( gdhA ), glutamine synthetase ( glnA ), phosphoenolpyruvate carboxylase ( ppc ), aspartate aminotransferase ( aspC ), transhydrogenase ( pntAB ), and l -arginine decarboxylase ( speA ) in the previously developed E. coli strain AUX4.…”