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- Title
Biosynthesis of Streptolidine Involved Two Unexpected Intermediates Produced by a Dihydroxylase and a Cyclase through Unusual Mechanisms.
- Authors
Chang, Chin ‐ Yuan; Lyu, Syue ‐ Yi; Liu, Yu ‐ Chen; Hsu, Ning ‐ Shian; Wu, Chih ‐ Chung; Tang, Cheng ‐ Fong; Lin, Kuan ‐ Hung; Ho, Jin ‐ Yuan; Wu, Chang ‐ Jer; Tsai, Ming ‐ Daw; Li, Tsung ‐ Lin
- Abstract
Streptothricin-F (STT-F), one of the early-discovered antibiotics, consists of three components, a β-lysine homopolymer, an aminosugar D-gulosamine, and an unusual bicyclic streptolidine. The biosynthesis of streptolidine is a long-lasting but unresolved puzzle. Herein, a combination of genetic/biochemical/structural approaches was used to unravel this problem. The STT gene cluster was first sequenced from a Streptomyces variant BCRC 12163, wherein two gene products OrfP and OrfR were characterized in vitro to be a dihydroxylase and a cyclase, respectively. Thirteen high-resolution crystal structures for both enzymes in different reaction intermediate states were snapshotted to help elucidate their catalytic mechanisms. OrfP catalyzes an FeII-dependent double hydroxylation reaction converting L-Arg into (3 R,4 R)-(OH)2- L-Arg via (3 S)-OH- L-Arg, while OrfR catalyzes an unusual PLP-dependent elimination/addition reaction cyclizing (3 R,4 R)-(OH)2- L-Arg to the six-membered (4 R)-OH-capreomycidine. The biosynthetic mystery finally comes to light as the latter product was incorporation into STT-F by a feeding experiment.
- Subjects
BIOSYNTHESIS; AMINO acids; INTERMEDIATES (Chemistry); HYDROXYLASES; CYCLASES; STREPTOTHRICIN
- Publication
Angewandte Chemie, 2014, Vol 126, Issue 7, p1974
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201307989