Evolution-guided engineering of trans-acyltransferase polyketide synthases.
Science
; 383(6689): 1312-1317, 2024 Mar 22.
Article
em 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
/
Proteínas Recombinantes de Fusão
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Aciltransferases
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Evolução Molecular Direcionada
/
Policetídeo Sintases
/
Policetídeos
Idioma:
En
Revista:
Science
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Suíça