(S)-3-aminopiperidine-2,6-dione is a biosynthetic intermediate of microbial blue pigment indigoidine.
mLife
; 1(2): 146-155, 2022 Jun.
Article
in En
| MEDLINE
| ID: mdl-38817675
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
MLife
Year:
2022
Document type:
Article