Engineering of Escherichia coli for the synthesis of N-hydroxycinnamoyl tryptamine and serotonin

J Ind Microbiol Biotechnol. 2017 Nov;44(11):1551-1560. doi: 10.1007/s10295-017-1975-3. Epub 2017 Aug 17.

Abstract

Plants synthesize various phenol amides. Among them, hydroxycinnamoyl (HC) tryptamines and serotonins exhibit antioxidant, anti-inflammatory, and anti-atherogenic activities. We synthesized HC-tryptamines and HC-serotonin from several HCs and either tryptamine or serotonin using Escherichia coli harboring the 4CL (4-coumaroyl CoA ligase) and CaHCTT [hydroxycinnamoyl-coenzyme A:serotonin N-(hydroxycinnamoyl)transferase] genes. E. coli was engineered to synthesize N-cinnamoyl tryptamine from glucose. TDC (tryptophan decarboxylase) and PAL (phenylalanine ammonia lyase) along with 4CL and CaHCTT were introduced into E. coli and the phenylalanine biosynthetic pathway of E. coli was engineered. Using this strategy, approximately 110.6 mg/L of N-cinnamoyl tryptamine was synthesized. By feeding 100 μM serotonin into the E. coli culture, which could induce the synthesis of cinnamic acid or p-coumaric acid, more than 99 μM of N-cinnamoyl serotonin and N-(p-coumaroyl) serotonin were synthesized.

Keywords: N-Hydroxycinnamoyl serotonin; N-Hydroxycinnamoyl tryptamine.

MeSH terms

  • Aromatic-L-Amino-Acid Decarboxylases / genetics
  • Aromatic-L-Amino-Acid Decarboxylases / metabolism
  • Bacillus / enzymology
  • Bacillus / genetics
  • Biosynthetic Pathways
  • Catharanthus / enzymology
  • Catharanthus / genetics
  • Cinnamates / metabolism
  • Cloning, Molecular
  • Coumaric Acids / metabolism
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Microorganisms, Genetically-Modified*
  • Phenylalanine
  • Phenylalanine Ammonia-Lyase / metabolism
  • Serotonin / biosynthesis*
  • Tryptamines / biosynthesis*

Substances

  • Cinnamates
  • Coumaric Acids
  • Tryptamines
  • cinnamic acid
  • Serotonin
  • Phenylalanine
  • Aromatic-L-Amino-Acid Decarboxylases
  • Phenylalanine Ammonia-Lyase