Characterization of a flavin-containing monooxygenase from Corynebacterium glutamicum and its application to production of indigo and indirubin

Biotechnol Lett. 2015 Aug;37(8):1637-44. doi: 10.1007/s10529-015-1824-2. Epub 2015 Apr 8.

Abstract

Objective: To examine the role of a gene encoding flavin-containing monooxygenase (cFMO) from Corynebacterium glutamicum ATCC13032 when cloned and expressed in Escherichia coli for the production of indigo pigments.

Results: The blue pigments produced by recombinant E. coli were identified as indigo and indirubin. The cFMO was purified as a fused form with maltose-binding protein (MBP). The enzyme was optimal at 25 °C and pH 8. From absorption spectrum analysis, the cFMO was classified as a flavoprotein. FMO activity was strongly inhibited by 1 mM Cu(2+) and recovered by adding 1-10 mM EDTA. The enzyme catalyzed the oxidation of TMA, thiourea, and cysteamine, but not glutathione or cysteine. MBP-cFMO had an indole oxygenase activity through oxygenation of indole to indoxyl. The recombinant E. coli produced 685 mg indigo l(-1) and 103 mg indirubin l(-1) from 2.5 g L-tryptophan l(-1).

Conclusion: The results suggest the cFMO can be used for the microbial production of both indigo and indirubin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cloning, Molecular
  • Copper / metabolism
  • Corynebacterium glutamicum / enzymology*
  • Corynebacterium glutamicum / genetics
  • Enzyme Inhibitors / metabolism
  • Enzyme Stability
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Hydrogen-Ion Concentration
  • Indigo Carmine / metabolism*
  • Indoles / metabolism
  • Oxygenases / chemistry
  • Oxygenases / genetics
  • Oxygenases / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Spectrum Analysis
  • Temperature

Substances

  • Enzyme Inhibitors
  • Indoles
  • Recombinant Proteins
  • Copper
  • Indigo Carmine
  • Oxygenases
  • dimethylaniline monooxygenase (N-oxide forming)
  • indirubin