5-Aminolevulinic acid production in engineered Corynebacterium glutamicum via C<inf>5</inf> biosynthesis pathway

Ahmad Bazli Ramzi, Jeong Eun Hyeon, Seung Wook Kim, Chulhwan Park, Sung Ok Han

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

ALA (5-aminolevulinic acid) is an important intermediate in the synthesis of tetrapyrroles and the use of ALA has been gradually increasing in many fields, including medicine and agriculture. In this study, improved biological production of ALA in Corynebacterium glutamicum was achieved by overexpressing glutamate-initiated C<inf>5</inf> pathway. For this purpose, copies of the glutamyl t-RNA reductase HemA from several bacteria were mutated by site-directed mutagenesis of which a HemA version from Salmonella typhimurium exhibited the highest ALA production. Cultivation of the HemA-expressing strain produced approximately 204mg/L of ALA, while co-expression with HemL (glutamate-1-semialdehyde aminotransferase) increased ALA concentration to 457mg/L, representing 11.6- and 25.9-fold increases over the control strain (17mg/L of ALA). Further effects of metabolic perturbation were investigated, leading to penicillin addition that further improves ALA production to 584mg/L. In an optimized flask fermentation, engineered C. glutamicum strains expressing the HemA and hemAL operon produced up to 1.1 and 2.2g/L ALA, respectively, under glutamate-producing conditions. The final yields represent 10.7- and 22.0-fold increases over the control strain (0.1g/L of ALA). From these findings, ALA biosynthesis from glucose was successfully demonstrated and this study is the first to report ALA overproduction in C. glutamicum via metabolic engineering.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalEnzyme and Microbial Technology
Volume81
DOIs
Publication statusPublished - 2015 Dec 1

Keywords

  • 5-Aminolevulinic acid
  • C<inf>5</inf> pathway
  • Corynebacterium glutamicum
  • Glutamate
  • Glutamyl t-RNA reductase

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Applied Microbiology and Biotechnology

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