Discovery of lysine hydroxylases in the clavaminic acid synthase-like superfamily for efficient hydroxylysine bioproduction

Ryotaro Hara*, Kai Yamagata, Ryoma Miyake, Hiroshi Kawabata, Hisatoshi Uehara, Kuniki Kino

*この研究の対応する著者

研究成果: Article査読

12 被引用数 (Scopus)

抄録

Hydroxylation via COH bond activation in the absence of any harmful oxidizing reagents is technically difficult in modern chemistry. In this work, we attempted to generate pharmaceutically important hydroxylysine from readily available L-lysine with L-lysine hydroxylases from diverse microorganisms. Clavaminic acid synthase-like superfamily gene mining and phylogenetic analysis led to the discovery of six biocatalysts, namely two L-lysine 3S-hydroxylases and four L-lysine 4Rhydroxylases, the latter of which partially matched known hydroxylases. Subsequent characterization of these hydroxylases revealed their capacity for regio- and stereoselective hydroxylation into either C-3 or C-4 positions of L-lysine, yielding (2S,3S)-3- hydroxylysine and (2S,4R)-4-hydroxylysine, respectively. To determine if these factors had industrial application, we performed a preparative production of both hydroxylysines under optimized conditions. For this, recombinant L-lysine hydroxylaseexpressing Escherichia coli cells were used as a biocatalyst for L-lysine bioconversion. In batch-scale reactions, 531 mM (86.1 g/liter) (2S,3S)-3-hydroxylysine was produced from 600 mM L-lysine with an 89% molar conversion after a 52-h reaction, and 265 mM (43.0 g/liter) (2S,4R)-4-hydroxylysine was produced from 300 mM L-lysine with a molar conversion of 88% after 24 h. This report demonstrates the highly efficient production of hydroxylysines using lysine hydroxylases, which may contribute to future industrial bioprocess technologies.

本文言語English
論文番号e00693-17
ジャーナルApplied and Environmental Microbiology
83
17
DOI
出版ステータスPublished - 2017 9月 1

ASJC Scopus subject areas

  • バイオテクノロジー
  • 食品科学
  • 応用微生物学とバイオテクノロジー
  • 生態学

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