Biosynthesis of Glidomides and Elucidation of Different Mechanisms for Formation of ß-OH Amino Acid Building Blocks.
Angew Chem Int Ed Engl
; 61(35): e202203591, 2022 08 26.
Article
em En
| MEDLINE
| ID: mdl-35689369
ABSTRACT
Nonribosomal peptide synthetases (NRPSs) can incorporate nonproteinogenic amino acids into peptidyl backbones to increase structural diversity. Genome mining of Schlegelella brevitalea led to the identification of a class of linear lipoheptapeptides, glidomides, featuring two unusual residues threo-ß-OH-L-His and threo-ß-OH-D-Asp. The ß-hydroxylation of Asp and His is catalyzed by the nonheme FeII /α-ketoglutarate-dependent ß-hydroxylases GlmD and GlmF, respectively. GlmD independently catalyzes the hydroxylation of L-Asp to primarily produce threo-ß-OH-L-Asp on the thiolation domain, and then undergoes epimerization to form threo-ß-OH-D-Asp in the final products. However, ß-hydroxylation of His requires the concerted action of GlmF and the interface (I) domain, a novel condensation domain family clade. The key sites of I domain for interaction with GlmF were identified, suggesting that the mechanism for hydroxylation of His depends on the collaboration between hydroxylase and NRPS.
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Base de dados:
MEDLINE
Assunto principal:
Peptídeo Sintases
/
Aminoácidos
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article