Evolution-guided engineering of trans-acyltransferase polyketide synthases.
Science
; 383(6689): 1312-1317, 2024 Mar 22.
Article
en En
| MEDLINE
| ID: mdl-38513027
ABSTRACT
Bacterial multimodular polyketide synthases (PKSs) are giant enzymes that generate a wide range of therapeutically important but synthetically challenging natural products. Diversification of polyketide structures can be achieved by engineering these enzymes. However, notwithstanding successes made with textbook cis-acyltransferase (cis-AT) PKSs, tailoring such large assembly lines remains challenging. Unlike textbook PKSs, trans-AT PKSs feature an extraordinary diversity of PKS modules and commonly evolve to form hybrid PKSs. In this study, we analyzed amino acid coevolution to identify a common module site that yields functional PKSs. We used this site to insert and delete diverse PKS parts and create 22 engineered trans-AT PKSs from various pathways and in two bacterial producers. The high success rates of our engineering approach highlight the broader applicability to generate complex designer polyketides.
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MEDLINE
Asunto principal:
Proteínas Bacterianas
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Proteínas Recombinantes de Fusión
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Aciltransferasas
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Evolución Molecular Dirigida
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Sintasas Poliquetidas
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Policétidos
Idioma:
En
Revista:
Science
Año:
2024
Tipo del documento:
Article