Reference - Detail
| RRC ID | 88721 |
|---|---|
| Author | Kawai S, Moriga K, Nirdnoy W, Hara R, Ogawa J, Katsuyama Y, Ohnishi Y. |
| Title | Identification of Two Distinct Stereoselective Lysine 5-Hydroxylases by Genome Mining Based on Alazopeptin Biosynthetic Enzymes. |
| Journal | Chemistry |
| Abstract |
Enzymes that catalyze regioselective and stereoselective hydroxylation of amino acids are useful tools for the synthesis of pharmaceuticals. AzpK is an unprecedented lysine 5-hydroxylase that is involved in alazopeptin biosynthesis, although its enzymatic activity has not been confirmed in vitro. Here, we identified two α-ketoglutarate/Fe2+-dependent dioxygenases in Actinosynnema mirum and Pseudomonas psychrotolerans (Am_AzpK2 and Pp_AzpK2, respectively) as lysine 5-hydroxylases, using genome mining based on the alazopeptin biosynthetic gene cluster. Interestingly, Am_AzpK2 and Pp_AzpK2 synthesized different isomers, (2S,5S)- and (2S,5R)-5-hydroxylysine, respectively. We also identified two AzpJ homologs as the dehydrogenases that specifically recognize the hydroxy groups of (2S,5S)- and (2S,5R)-5-hydroxylysine to synthesize a keto group. These dehydrogenases were shown to be useful tools for characterizing the stereochemistry of 5-hydroxylysine and evaluating the activity of lysine 5-hydroxylases. Furthermore, we identified three lysine 5-hydroxylases that synthesize (2S,5S)-5-hydroxylysine and four lysine 5-hydroxylases that synthesize (2S,5R)-5-hydroxylysine from the genome database. Genome scanning based on lysine 5-hydroxylases indicated the presence of undiscovered natural products with 5-hydroxylysine moieties. In conclusion, this study provides a fundamental technology for the stereoselective production of 5-hydroxylysine. Further analysis of the stereoselective lysine 5-hydroxylases would reveal how nature establishes highly stereoselective hydroxylation. |
| Volume | 31(20) |
| Pages | e202404790 |
| Published | 2025-4-4 |
| DOI | 10.1002/chem.202404790 |
| PMID | 39960436 |
| PMC | PMC11973848 |
| MeSH | Actinobacteria / enzymology Actinobacteria / genetics Hydroxylation Hydroxylysine / chemistry Hydroxylysine / metabolism Ketoglutaric Acids / chemistry Ketoglutaric Acids / metabolism Lysine* / analogs & derivatives Lysine* / chemistry Lysine* / metabolism Mixed Function Oxygenases* / chemistry Mixed Function Oxygenases* / genetics Mixed Function Oxygenases* / metabolism Multigene Family Pseudomonas / enzymology Pseudomonas / genetics Stereoisomerism Substrate Specificity |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 8 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| General Microbes | JCM3225 |