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Synthesis of cinnabarinic acid by metabolically engineered Pseudomonas chlororaphis GP72.

Abstract

Cinnabarinic acid is a valuable phenoxazinone that has broad applications in the pharmaceutical, chemical, and dyeing industries. However, few studies have investigated the production of cinnabarinic acid or its derivatives using genetically engineered microorganisms. Herein, an efficient synthetic pathway of cinnabarinic acid was designed and constructed in Pseudomonas chlororaphis GP72 for the first tim, which was more straightforward and robust than the known eukaryotic biosynthetic pathways. First, we screened and identified trans-2,3-dihydro-3-hydroxyanthranilic acid (DHHA) dehydrogenases from Escherichia coli MG1655 (encoded by entA), Streptomyces sp. NRRL12068 (encoded by bomO) and Streptomyces chartreusis NRRL3882 (encoded by calB3) based on the structural similarity of the substrate and product, and the DHHA dehydrogenase encoded by calB3 was selected for the synthesis of cinnabarinic acid due to its high DHHA conversion rate. Subsequently, cinnabarinic acid was synthesized by the expression of the DHHA dehydrogenase CalB3 and the phenoxazinone synthase CotA in the DHHA-producing strain P. chlororaphis GP72, resulting in a cinnabarinic acid titer of 20.3 mg/L at 48 hr. Further fermentation optimization by the addition of Cu2+ , H2 O2 , and with adding glycerol increased cinnabarinic acid titer to 136.2 mg/L in shake flasks. The results indicate that P. chlororaphis GP72 may be engineered as a microbial cell factory to produce cinnabarinic acid or its derivatives from renewable bioresources.

Authors+Show Affiliations

State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China. National Experimental Teaching Center for Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.State Key Laboratory of Microbial Metabolism, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31317529

Citation

Yue, Sheng-Jie, et al. "Synthesis of Cinnabarinic Acid By Metabolically Engineered Pseudomonas Chlororaphis GP72." Biotechnology and Bioengineering, 2019.
Yue SJ, Song C, Li S, et al. Synthesis of cinnabarinic acid by metabolically engineered Pseudomonas chlororaphis GP72. Biotechnol Bioeng. 2019.
Yue, S. J., Song, C., Li, S., Huang, P., Guo, S. Q., Hu, H. B., ... Zhang, X. H. (2019). Synthesis of cinnabarinic acid by metabolically engineered Pseudomonas chlororaphis GP72. Biotechnology and Bioengineering, doi:10.1002/bit.27118.
Yue SJ, et al. Synthesis of Cinnabarinic Acid By Metabolically Engineered Pseudomonas Chlororaphis GP72. Biotechnol Bioeng. 2019 Jul 17; PubMed PMID: 31317529.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis of cinnabarinic acid by metabolically engineered Pseudomonas chlororaphis GP72. AU - Yue,Sheng-Jie, AU - Song,Chen, AU - Li,Song, AU - Huang,Peng, AU - Guo,Shu-Qi, AU - Hu,Hong-Bo, AU - Wang,Wei, AU - Zhang,Xue-Hong, Y1 - 2019/07/17/ PY - 2019/04/29/received PY - 2019/07/10/revised PY - 2019/07/10/accepted PY - 2019/7/19/pubmed PY - 2019/7/19/medline PY - 2019/7/19/entrez KW - DHHA KW - Pseudomonas chlororaphis GP72 KW - cinnabarinic acid KW - renewable bioresources KW - synthetic pathway JF - Biotechnology and bioengineering JO - Biotechnol. Bioeng. N2 - Cinnabarinic acid is a valuable phenoxazinone that has broad applications in the pharmaceutical, chemical, and dyeing industries. However, few studies have investigated the production of cinnabarinic acid or its derivatives using genetically engineered microorganisms. Herein, an efficient synthetic pathway of cinnabarinic acid was designed and constructed in Pseudomonas chlororaphis GP72 for the first tim, which was more straightforward and robust than the known eukaryotic biosynthetic pathways. First, we screened and identified trans-2,3-dihydro-3-hydroxyanthranilic acid (DHHA) dehydrogenases from Escherichia coli MG1655 (encoded by entA), Streptomyces sp. NRRL12068 (encoded by bomO) and Streptomyces chartreusis NRRL3882 (encoded by calB3) based on the structural similarity of the substrate and product, and the DHHA dehydrogenase encoded by calB3 was selected for the synthesis of cinnabarinic acid due to its high DHHA conversion rate. Subsequently, cinnabarinic acid was synthesized by the expression of the DHHA dehydrogenase CalB3 and the phenoxazinone synthase CotA in the DHHA-producing strain P. chlororaphis GP72, resulting in a cinnabarinic acid titer of 20.3 mg/L at 48 hr. Further fermentation optimization by the addition of Cu2+ , H2 O2 , and with adding glycerol increased cinnabarinic acid titer to 136.2 mg/L in shake flasks. The results indicate that P. chlororaphis GP72 may be engineered as a microbial cell factory to produce cinnabarinic acid or its derivatives from renewable bioresources. SN - 1097-0290 UR - https://www.unboundmedicine.com/medline/citation/31317529/Synthesis_of_cinnabarinic_acid_by_metabolically_engineered_Pseudomonas_chlororaphis_GP72 L2 - https://doi.org/10.1002/bit.27118 DB - PRIME DP - Unbound Medicine ER -