Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Biosynthesis of 3-Hydroxy-5-Methyl-O-Methyltyrosine in the Saframycin/Safracin Biosynthetic Pathway

  • Fu, Cheng-Yu (School of Life Science and Technology, Xi'an Jiaotong University) ;
  • Tang, Man-Cheng (State Key Laboratory of Bio-Organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences) ;
  • Peng, Chao (State Key Laboratory of Bio-Organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences) ;
  • Li, Lei (State Key Laboratory of Bio-Organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences) ;
  • He, Yan-Ling (School of Life Science and Technology, Xi'an Jiaotong University) ;
  • Liu, Wen (State Key Laboratory of Bio-Organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences) ;
  • Tang, Gong-Li (State Key Laboratory of Bio-Organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences)
  • Published : 2009.05.31
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Abstract

The biosynthesis study of antibiotics saframycin (SFM) in Streptomyces lavendulae and safracin (SAC) in Pseudomonas fluorescens demonstrated that 3-hydroxy-S-methyl-O-methyltyrosine (3hSmOmTyr), a nonproteinogenic amino acid, is the precursor of the tetrahydroisoquinoline molecular core. In the biosynthetic gene cluster of SAC/SFM, sacD/sfmD encodes a protein with high homology to each other but no sequence similarity to other known enzymes; sacF/sfmM2 and sacG/sfmM3 encode methyltransferases for C-methylation and O-methylation; and sacE/sfinF encodes a small protein with significant sequence similarity to the MbtH-like proteins, which are frequently found in the biosynthetic pathways of non ribosomal peptide antibiotics and siderophores. To address their function, the biosynthetic cassette of 3h5mOmTyr was heterologously expressed in S. coelicolor and P. putida, and an in-frame deletion and complementation in trans were carried out. The results revealed that (i) SfmD catalyzes the hydroxylation of aromatic rings; (ii) sacD/sacF/sacG in the SAC gene cluster and sfmD/sfmM2/sfmM3 in the SFM cluster are sufficient for the biosynthesis of 3h5mOmTyr; and (iii) the mbtH-like gene is not required for the biosynthesis of the 3h5mOmTyr precursor.

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