Biosynthetic engineering of the antifungal, anti-MRSA auroramycin.
Microb Cell Fact
; 19(1): 3, 2020 Jan 06.
Article
em En
| MEDLINE
| ID: mdl-31906943
ABSTRACT
Using an established CRISPR-Cas mediated genome editing technique for streptomycetes, we explored the combinatorial biosynthesis potential of the auroramycin biosynthetic gene cluster in Streptomyces roseosporous. Auroramycin is a potent anti-MRSA polyene macrolactam. In addition, auroramycin has antifungal activities, which is unique among structurally similar polyene macrolactams, such as incednine and silvalactam. In this work, we employed different engineering strategies to target glycosylation and acylation biosynthetic machineries within its recently elucidated biosynthetic pathway. Auroramycin analogs with variations in C-, N- methylation, hydroxylation and extender units incorporation were produced and characterized. By comparing the bioactivity profiles of five of these analogs, we determined that unique disaccharide motif of auroramycin is essential for its antimicrobial bioactivity. We further demonstrated that C-methylation of the 3, 5-epi-lemonose unit, which is unique among structurally similar polyene macrolactams, is key to its antifungal activity.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Streptomyces
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Vias Biossintéticas
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Engenharia Metabólica
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Antibacterianos
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Antifúngicos
Idioma:
En
Revista:
Microb Cell Fact
Assunto da revista:
BIOTECNOLOGIA
/
MICROBIOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Singapura