Metabolic engineering of Corynebacterium glutamicum for methionine production by removing feedback inhibition and increasing NADPH level

2016 ◽  
Vol 109 (9) ◽  
pp. 1185-1197 ◽  
Author(s):  
Ying Li ◽  
Hua Cong ◽  
Bingnan Liu ◽  
Jinzhu Song ◽  
Xueying Sun ◽  
...  
Keyword(s):  
Metabolic Engineering ◽  
Corynebacterium Glutamicum ◽  
Feedback Inhibition

scholarly journals Metabolic engineering of Corynebacterium glutamicum for producing branched chain amino acids

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Shengzhu Yu ◽  
Bo Zheng ◽  
Zhenya Chen ◽  
Yi-Xin Huo
Keyword(s):  
Amino Acids ◽  
Metabolic Engineering ◽  
Corynebacterium Glutamicum ◽  
Animal Feed ◽  
Feedback Inhibition ◽  
Value Added ◽  
Branched Chain Amino Acids ◽  
High Yield ◽  
Acetohydroxy Acid Synthase ◽  
Branched Chain

Abstract Background Branched chain amino acids (BCAAs) are widely applied in the food, pharmaceutical, and animal feed industries. Traditional chemical synthetic and enzymatic BCAAs production in vitro has been hampered by expensive raw materials, harsh reaction conditions, and environmental pollution. Microbial metabolic engineering has attracted considerable attention as an alternative method for BCAAs biosynthesis because it is environmentally friendly and delivers high yield. Main text Corynebacterium glutamicum (C. glutamicum) possesses clear genetic background and mature gene manipulation toolbox, and has been utilized as industrial host for producing BCAAs. Acetohydroxy acid synthase (AHAS) is a crucial enzyme in the BCAAs biosynthetic pathway of C. glutamicum, but feedback inhibition is a disadvantage. We therefore reviewed AHAS modifications that relieve feedback inhibition and then investigated the importance of AHAS modifications in regulating production ratios of three BCAAs. We have comprehensively summarized and discussed metabolic engineering strategies to promote BCAAs synthesis in C. glutamicum and offer solutions to the barriers associated with BCAAs biosynthesis. We also considered the future applications of strains that could produce abundant amounts of BCAAs. Conclusions Branched chain amino acids have been synthesized by engineering the metabolism of C. glutamicum. Future investigations should focus on the feedback inhibition and/or transcription attenuation mechanisms of crucial enzymes. Enzymes with substrate specificity should be developed and applied to the production of individual BCAAs. The strategies used to construct strains producing BCAAs provide guidance for the biosynthesis of other high value-added compounds.

An improved shuttle vector constructed for metabolic engineering research in Corynebacterium glutamicum

Plasmid ◽  
2010 ◽  
Vol 64 (2) ◽  
pp. 85-91 ◽  
Author(s):  
Daqing Xu ◽  
Yanzhen Tan ◽  
Feng Shi ◽  
Xiaoyuan Wang
Keyword(s):  
Metabolic Engineering ◽  
Corynebacterium Glutamicum ◽  
Shuttle Vector ◽  
Engineering Research

Metabolic Engineering of Corynebacterium glutamicum

2021 ◽  
pp. 403-468
Author(s):  
Judith Becker ◽  
Christoph Wittmann
Keyword(s):  
Metabolic Engineering ◽  
Corynebacterium Glutamicum

Metabolic Engineering of Lysine Producing Corynebacterium glutamicum Strains

2020 ◽  
Vol 54 (2) ◽  
pp. 137-146
Author(s):  
G. S. Andriiash ◽  
O. S. Sekan ◽  
O. O. Tigunova ◽  
Ya. B. Blume ◽  
S. M. Shulga
Keyword(s):  
Metabolic Engineering ◽  
Corynebacterium Glutamicum

scholarly journals PII Signal Transduction Protein GlnK Alleviates Feedback Inhibition of N-Acetyl-L-Glutamate Kinase by L-Arginine in Corynebacterium glutamicum

2020 ◽  
Vol 86 (8) ◽  
Author(s):  
Meijuan Xu ◽  
Mi Tang ◽  
Jiamin Chen ◽  
Taowei Yang ◽  
Xian Zhang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Amino Acid ◽  
Glutamic Acid ◽  
Corynebacterium Glutamicum ◽  
Feedback Inhibition ◽  
Amino Acid Biosynthesis ◽  
Arginine Biosynthesis ◽  
Acid Biosynthesis ◽  
Content Type ◽  
Pii Protein

ABSTRACT PII signal transduction proteins are ubiquitous and highly conserved in bacteria, archaea, and plants and play key roles in controlling nitrogen metabolism. However, research on biological functions and regulatory targets of PII proteins remains limited. Here, we illustrated experimentally that the PII protein Corynebacterium glutamicum GlnK (CgGlnK) increased l-arginine yield when glnK was overexpressed in Corynebacterium glutamicum. Data showed that CgGlnK regulated l-arginine biosynthesis by upregulating the expression of genes of the l-arginine metabolic pathway and interacting with N-acetyl-l-glutamate kinase (CgNAGK), the rate-limiting enzyme in l-arginine biosynthesis. Further assays indicated that CgGlnK contributed to alleviation of the feedback inhibition of CgNAGK caused by l-arginine. In silico analysis of the binding interface of CgGlnK-CgNAGK suggested that the B and T loops of CgGlnK mainly interacted with C and N domains of CgNAGK. Moreover, F11, R47, and K85 of CgGlnK were identified as crucial binding sites that interact with CgNAGK via hydrophobic interaction and H bonds, and these interactions probably had a positive effect on maintaining the stability of the complex. Collectively, this study reveals PII-NAGK interaction in nonphotosynthetic microorganisms and further provides insights into the regulatory mechanism of PII on amino acid biosynthesis in corynebacteria. IMPORTANCE Corynebacteria are safe industrial producers of diverse amino acids, including l-glutamic acid and l-arginine. In this study, we showed that PII protein GlnK played an important role in l-glutamic acid and l-arginine biosynthesis in C. glutamicum. Through clarifying the molecular mechanism of CgGlnK in l-arginine biosynthesis, the novel interaction between CgGlnK and CgNAGK was revealed. The alleviation of l-arginine inhibition of CgNAGK reached approximately 48.21% by CgGlnK addition, and the semi-inhibition constant of CgNAGK increased 1.4-fold. Furthermore, overexpression of glnK in a high-yield l-arginine-producing strain and fermentation of the recombinant strain in a 5-liter bioreactor led to a remarkably increased production of l-arginine, 49.978 g/liter, which was about 22.61% higher than that of the initial strain. In conclusion, this study provides a new strategy for modifying amino acid biosynthesis in C. glutamicum.

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