title: A New Strategy for Production of 5-Aminolevulinic Acid in Recombinant Corynebacterium glutamicum with High Yield.
abstract: 5-Aminolevulinic acid (ALA), a nonprotein amino acid involved in tetrapyrrole synthesis, has been widely applied in agriculture, medicine, and food production. Many engineered metabolic pathways have been constructed; however, the production yields are still low. In this study, several 5-aminolevulinic acid synthases (ALASs) from different sources were evaluated and compared with respect to their ALA production capacities in an engineered Corynebacterium glutamicum CgS1 strain that can accumulate succinyl-coenzyme A (CoA). A codon-optimized ALAS from Rhodobacter capsulatus SB1003 displayed the best potential. Recombinant strain CgS1/pEC-SB produced 7.6 g/liter ALA using a mineral salt medium in a fed-batch fermentation mode. Employing two-stage fermentation, 12.46 g/liter ALA was produced within 17 h, with a productivity of 0.73 g/liter/h, in recombinant C. glutamicum Through overexpression of the heterologous nonspecific ALA exporter RhtA from Escherichia coli, the titer was further increased to 14.7 g/liter. This indicated that strain CgS1/pEC-SB-rhtA holds attractive industrial application potential for the future.
  
  
  OBJECTIVE
  In this study, a two-stage fermentation strategy was used for production of the value-added nonprotein amino acid 5-aminolevulinic acid from glucose and glycine in a generally recognized as safe (GRAS) host,Corynebacterium glutamicum The ALA titer represented the highest in the literature, to our knowledge. This high production capacity, combined with the potential easy downstream processes, made the recombinant strain an attractive candidate for industrial use in the future.
authors.affiliation: State Key Laboratory of Microbial Technology, Shandong University, Jinan, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Microbial Technology, Shandong University, Jinan, People's Republic of China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Liu
authors.affiliation: National Glycoengineering Center, Shandong University, Jinan, People's Republic of China.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Microbial Technology, Shandong University, Jinan, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Microbial Technology, Shandong University, Jinan, People's Republic of China qiqi20011983@gmail.com.|National Glycoengineering Center, Shandong University, Jinan, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Microbial Technology, Shandong University, Jinan, People's Republic of China.
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Qi
mesh_terms: D000214:Acyl Coenzyme A / Q000096:biosynthesis; D000596:Amino Acids / Q000378:metabolism; D000622:Aminolevulinic Acid / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D061249:Batch Cell Culture Techniques / Q000379:methods; D053898:Biosynthetic Pathways; D048230:Corynebacterium glutamicum / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D005285:Fermentation; D007218:Industrial Microbiology / Q000379:methods; D060847:Metabolic Engineering / Q000379:methods
chemical_list: D000214:Acyl Coenzyme A; D000596:Amino Acids; D001426:Bacterial Proteins; D000622:Aminolevulinic Acid; C012046:succinyl-coenzyme A