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Biosynthesis of Two Hydroxybenzoic Acid-Amine Conjugates in Engineered Escherichia coli

Journal of Microbiology and Biotechnology 2019년 29권 10호 p.1636 ~ 1643
신평균 ( Kim Song-Yi ) - Konkuk University Department of Bioscience and Biotechnology

 ( Kim Han ) - Konkuk University Department of Bioscience and Biotechnology
 ( Kim Bong-Gyu ) - Gyeongnam National University of Science and Technology Department of Forest Resources
 ( Ahn Joong-Hoon ) - Konkuk University Department of Bioscience and Biotechnology

Abstract


Two hydroxybenzoyl amines, 4-hydroxybenzoyl tyramine (4-HBT) and N-2-hydroxybenzoyl tryptamine (2-HBT), were synthesized using Escherichia coli. While 4-HBT was reported to demonstrate anti-atherosclerotic activity, 2-HBT showed anticonvulsant and antinociceptive activities. We introduced genes chorismate pyruvate-lyase (ubiC), tyrosine decarboxylase (TyDC), isochorismate synthase (entC), isochorismate pyruvate lyase (pchB), and tryptophan decarboxylase (TDC) for each substrate, 4-hydroxybenzoic acid (4-HBA), tyramine, 2-hydroxybenzoic acid (2-HBA), and tryptamine, respectively, in E. coli. Genes for CoA ligase (hbad) and amide formation (CaSHT and OsHCT) were also introduced to form hydroxybenzoic acid and amine conjugates. In addition, we engineered E. coli to provide increased substrates. These approaches led to the yield of 259.3 mg/l 4-HBT and 227.2 mg/l 2-HBT and could be applied to synthesize diverse bioactive hydroxybenzoyl amine conjugates.

키워드

Hydroxybenzoic acid; N-2-hydroxybenzoyl tryptamine; 4-hydroxybenzoyl tyramine; metabolic engineering
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