Genetic Engineering in Combination with Semi-Synthesis Leads to a New Route for Gram-Scale Production of the Immunosuppressive Natural Product Brasilicardinâ
A.
Angew Chem Int Ed Engl
; 60(24): 13536-13541, 2021 06 07.
Article
em En
| MEDLINE
| ID: mdl-33768597
ABSTRACT
Brasilicardinâ
A (1) consists of an unusual anti/syn/anti-perhydrophenanthrene skeleton with a carbohydrate side chain and an amino acid moiety. It exhibits potent immunosuppressive activity, yet its mode of action differs from standard drugs that are currently in use. Further pre-clinical evaluation of this promising, biologically active natural product is hampered by restricted access to the ready material, as its synthesis requires both a low-yielding fermentation process using a pathogenic organism and an elaborate, multi-step total synthesis. Our semi-synthetic approach included a) the heterologous expression of the brasilicardinâ
A gene cluster in different non-pathogenic bacterial strains producing brasilicardinâ
A aglycone (5) in excellent yield and b) the chemical transformation of the aglycone 5 into the trifluoroacetic acid salt of brasilicardinâ
A (1 a) via a short and straightforward five-steps synthetic route. Additionally, we report the first preclinical data for brasilicardinâ
A.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Engenharia Genética
/
Aminoglicosídeos
/
Imunossupressores
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article