The biosynthetic investigations of microbial natural products continuously provide powerful biocatalysts for the preparation of valuable chemicals.Practical methods for preparing(S)-3-aminopiperidine-2,6-dione(2),the ...The biosynthetic investigations of microbial natural products continuously provide powerful biocatalysts for the preparation of valuable chemicals.Practical methods for preparing(S)-3-aminopiperidine-2,6-dione(2),the pharmacophore of thalidomide(1)and its analog drugs,are highly desired.To develop a biocatalyst for producing(S)-2,we dissected the domain functions of IdgS,which is responsible for the biosynthesis of indigoidine(3),a microbial blue pigment that consists of two 2-like moieties.Our data supported that the L-glutamine tethered to the indigoidine assembly line is first offloaded and cyclized by the thioesterase domain to form(S)-2,which is then dehydrogenated by the oxidation(Ox)domain and finally dimerized to yield 3.Based on this,we developed an IdgS-derived enzyme biocatalyst,IdgS-Ox^(*)R539A,for preparing enantiomerically pure(S)-2.As a proof of concept,one-pot chemoenzymatic synthesis of 1 was achieved by combining the biocatalytic and chemical approaches.展开更多
基金supported in part by the National Key R&D Program of China(2020YFA0907700)the NSFC grants(32025002 and 31522001).
文摘The biosynthetic investigations of microbial natural products continuously provide powerful biocatalysts for the preparation of valuable chemicals.Practical methods for preparing(S)-3-aminopiperidine-2,6-dione(2),the pharmacophore of thalidomide(1)and its analog drugs,are highly desired.To develop a biocatalyst for producing(S)-2,we dissected the domain functions of IdgS,which is responsible for the biosynthesis of indigoidine(3),a microbial blue pigment that consists of two 2-like moieties.Our data supported that the L-glutamine tethered to the indigoidine assembly line is first offloaded and cyclized by the thioesterase domain to form(S)-2,which is then dehydrogenated by the oxidation(Ox)domain and finally dimerized to yield 3.Based on this,we developed an IdgS-derived enzyme biocatalyst,IdgS-Ox^(*)R539A,for preparing enantiomerically pure(S)-2.As a proof of concept,one-pot chemoenzymatic synthesis of 1 was achieved by combining the biocatalytic and chemical approaches.
