Production of a novel O-methyl-isoflavone by regioselective sequential hydroxylation and O-methylation reactions in Streptomyces avermitilis host system

Biotechnol Bioeng. 2013 Oct;110(10):2591-9. doi: 10.1002/bit.24931. Epub 2013 Apr 26.

Abstract

Distinct isoflavone O-methyltransferases (IOMTs) from Streptomyces species were isolated and expressed using S. avermitilis host system. Previously reported isoflavone 7-O-methyltransferases (I7OMTs, E.C. 2.1.1.150) and two putative O-methyltransferases (OMTs) from Saccharopolyspora erythraea were selected by comparative sequence grouping and expressed in S. avermitilisΔSaOMT2 under the control of constitutive ermE promoter. During whole-cell biotransformation of 4',7-dihydroxyisoflavone (daidzein) by constructed recombinant strains, production of O-methylated daidzein was investigated. S. avermitilisΔSaOMT2::SeOMT3 (SeOMT3) produced 7-methoxy-4'-hydroxyisoflavone (7-OMD) with 4.5% of low conversion yield due to competitive oxidation reactions. However, SeOMT3 could produce a novel 4',7-dihydroxy-3'-methoxyisoflavone (3'-OMD) (<1%) resulted from subsequent 3'-O-methylation of 3',4',7-trihydroxyisoflavone (3'-OHD) which was a hydroxylated product catalyzed by oxygenases. Although external addition of SAM did not change the conversion yield of O-methylation reaction, co-expression of SAM synthetase gene (metK) with SeOMT3 greatly induced the regiospecific O-methylation reaction at 3'-hydroxyl group with final conversion of 12.1% using 0.1 mM of daidzein.

Keywords: O-methyltransferase; SAM; Streptomyces; daidzein; metK; oxygenase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Biotechnology
  • Gas Chromatography-Mass Spectrometry
  • Hydroxylation
  • Isoflavones / analysis
  • Isoflavones / chemistry
  • Isoflavones / metabolism*
  • Methionine Adenosyltransferase / genetics
  • Methionine Adenosyltransferase / metabolism
  • Methylation
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Molecular Sequence Data
  • Phylogeny
  • S-Adenosylmethionine / metabolism
  • Sequence Alignment
  • Stereoisomerism
  • Streptomyces / classification
  • Streptomyces / enzymology*
  • Streptomyces / genetics
  • Streptomyces / metabolism*

Substances

  • Bacterial Proteins
  • Isoflavones
  • daidzein
  • S-Adenosylmethionine
  • Methyltransferases
  • Methionine Adenosyltransferase