6NSD

Tar14, tryptophan C-6 flavin-dependent halogenase (chlorinase) from taromycin biosynthesis

6NSD の概要

• エントリーDOI: 10.2210/pdb6nsd/pdb
• 分子名称: Tryptophan halogenase, FLAVIN-ADENINE DINUCLEOTIDE, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: halogenase, flavin, tryptophan, taromycin, biosynthetic protein
• 由来する生物種: Saccharomonospora sp. CNQ490
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 123290.81

構造登録者

Luhavaya, H.,Chekan, J.R.,Moore, B.S. (登録日: 2019-01-24, 公開日: 2019-04-24, 最終更新日: 2023-10-11)

主引用文献

Luhavaya, H.,Sigrist, R.,Chekan, J.R.,McKinnie, S.M.K.,Moore, B.S.
Biosynthesis of l-4-Chlorokynurenine, an Antidepressant Prodrug and a Non-Proteinogenic Amino Acid Found in Lipopeptide Antibiotics.
Angew.Chem.Int.Ed.Engl., 58:8394-8399, 2019

PubMed Abstract: l-4-Chlorokynurenine (l-4-Cl-Kyn) is a neuropharmaceutical drug candidate that is in development for the treatment of major depressive disorder. Recently, this amino acid was naturally found as a residue in the lipopeptide antibiotic taromycin. Herein, we report the unprecedented conversion of l-tryptophan into l-4-Cl-Kyn catalyzed by four enzymes in the taromycin biosynthetic pathway from the marine bacterium Saccharomonospora sp. CNQ-490. We used genetic, biochemical, structural, and analytical techniques to establish l-4-Cl-Kyn biosynthesis, which is initiated by the flavin-dependent tryptophan chlorinase Tar14 and its flavin reductase partner Tar15. This work revealed the first tryptophan 2,3-dioxygenase (Tar13) and kynurenine formamidase (Tar16) enzymes that are selective for chlorinated substrates. The substrate scope of Tar13, Tar14, and Tar16 was examined and revealed intriguing promiscuity, thereby opening doors for the targeted engineering of these enzymes as useful biocatalysts.

PubMed: 30963655
DOI: 10.1002/anie.201901571

実験手法

X-RAY DIFFRACTION (1.74 Å)