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5-Aminolevulinic acid production in engineered Corynebacterium glutamicum via C-5 biosynthesis pathway

Authors
Ramzi, Ahmad BazliHyeon, Jeong EunKim, Seung WookPark, ChulhwanHan, Sung Ok
Issue Date
12월-2015
Publisher
ELSEVIER SCIENCE INC
Keywords
5-Aminolevulinic acid; Corynebacterium glutamicum; C-5 pathway; Glutamyl t-RNA reductase; Glutamate
Citation
ENZYME AND MICROBIAL TECHNOLOGY, v.81, pp.1 - 7
Indexed
SCIE
SCOPUS
Journal Title
ENZYME AND MICROBIAL TECHNOLOGY
Volume
81
Start Page
1
End Page
7
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/91667
DOI
10.1016/j.enzmictec.2015.07.004
ISSN
0141-0229
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-5 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 204 mg/L of ALA, while co-expression with HemL (glutamate-1-semialdehyde aminotransferase) increased ALA concentration to 457 mg/L, representing 11.6- and 25.9-fold increases over the control strain (17 mg/L of ALA). Further effects of metabolic perturbation were investigated, leading to penicillin addition that further improves ALA production to 584 mg/L. In an optimized flask fermentation, engineered C. glutamicum strains expressing the HemA and hemAL operon produced up to 1.1 and 2.2 g/L ALA, respectively, under glutamate-producing conditions. The final yields represent 10.7- and 22.0-fold increases over the control strain (0.1 g/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. (C) 2015 Elsevier Inc. All rights reserved.
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