Publisher： John Wiley & Sons Inc
E-ISSN： 1521-3757|126|7|1974-1979
ISSN： 0044-8249
Source： ANGEWANDTE CHEMIE, Vol.126, Iss.7, 2014-02, pp. : 1974-1979
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Abstract
AbstractStreptothricin‐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 (3R,4R)‐(OH)2‐L‐Arg via (3S)‐OH‐L‐Arg, while OrfR catalyzes an unusual PLP‐dependent elimination/addition reaction cyclizing (3R,4R)‐(OH)2‐L‐Arg to the six‐membered (4R)‐OH‐capreomycidine. The biosynthetic mystery finally comes to light as the latter product was incorporation into STT‐F by a feeding experiment.
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