Biosynthesis of ß-lactam nuclei in yeast.
Metab Eng
; 72: 56-65, 2022 07.
Article
em En
| MEDLINE
| ID: mdl-35245651
ABSTRACT
We have engineered brewer's yeast as a general platform for de novo synthesis of diverse ß-lactam nuclei starting from simple sugars, thereby enabling ready access to a number of structurally different antibiotics of significant pharmaceutical importance. The biosynthesis of ß-lactam nuclei has received much attention in recent years, while rational engineering of non-native antibiotics-producing microbes to produce ß-lactam nuclei remains challenging. Benefited by the integration of heterologous biosynthetic pathways and rationally designed enzymes that catalyze hydrolysis and ring expansion reactions, we succeeded in constructing synthetic yeast cell factories which produce antibiotic cephalosporin C (CPC, 170.1 ± 4.9 µg/g DCW) and the downstream ß-lactam nuclei, including 6-amino penicillanic acid (6-APA, 5.3 ± 0.2 mg/g DCW), 7-amino cephalosporanic acid (7-ACA, 6.2 ± 1.1 µg/g DCW) as well as 7-amino desacetoxy cephalosporanic acid (7-ADCA, 1.7 ± 0.1 mg/g DCW). This work established a Saccharomyces cerevisiae platform capable of synthesizing multiple ß-lactam nuclei by combining natural and artificial enzymes, which serves as a metabolic tool to produce valuable ß-lactam intermediates and new antibiotics.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Saccharomyces cerevisiae
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Beta-Lactamas
Idioma:
En
Revista:
Metab Eng
Assunto da revista:
ENGENHARIA BIOMEDICA
/
METABOLISMO
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China