Enhancing 5-aminolevulinic acid tolerance and production by engineering the antioxidant defense system of Escherichia coli.

Authors:
Jiuzhou Chen
Jiuzhou Chen
Jiangnan University
China
Yu Wang
Yu Wang
Peking University People's Hospital
China
Lixian Wang
Lixian Wang
Institute of Animal Science
China
Xuan Guo
Xuan Guo
Rice University
United States
Ning Chen
Ning Chen
Capital Medical University
China
Ping Zheng
Ping Zheng
Zhejiang University
China
Jibin Sun
Jibin Sun
Hamburg University of Technology
Germany

Biotechnol Bioeng 2019 Apr 1. Epub 2019 Apr 1.

Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.

5-Aminolevulinic acid (ALA) is a value-added compound with potential applications in the fields of agriculture and medicine. Although massive efforts have recently been devoted to building microbial producers of ALA through metabolic engineering, few studies focused on the cellular response and tolerance to ALA. In this study, we demonstrated that ALA caused severe cell damage and morphology change of Escherichia coli via generating reactive oxygen species (ROS), which were further determined to be mainly hydrogen peroxide and superoxide anion radical. ALA treatment activated the native antioxidant defense system by upregulating catalase (CAT) and superoxide dismutase (SOD) expression to combat ROS. Further overexpressing CAT (encoded by katG and katE) and SOD (encoded by sodA, sodB, and sodC) not only improved ALA tolerance but also its production level. Notably, coexpression of katE and sodB in an ALA synthase expressing strain enhanced the biomass and final ALA titer by 81% and 117% (11.5 g/L) in a 5 L bioreactor, respectively. This study demonstrates the importance of tolerance engineering in strain development. Reinforcing the antioxidant defense system holds promise to improve the bioproduction of chemicals that cause oxidative stress.

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Source
http://dx.doi.org/10.1002/bit.26981DOI Listing
April 2019

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