Computation-driven redesign of an NRPS-like carboxylic acid reductase improves activity and selectivity DOI Creative Commons
Kun Shi, Ju‐Mou Li,

Mu-Qiang Wang

и другие.

Science Advances, Год журнала: 2024, Номер 10(48)

Опубликована: Ноя. 29, 2024

Engineering nonribosomal peptide synthetases (NRPSs) has been a “holy grail” in synthetic biology due to their modular nature and limited understanding of catalytic mechanisms. Here, we reported computational redesign the “gate-keeper” adenylation domain model NRPS-like enzyme carboxylic acid reductases (CARs) by using approximate mechanism-based geometric criteria Rosetta energy score. Notably, Mab CAR3 mutants ACA-1 ACA-4 displayed remarkable improvement efficiency ( k cat / K M ) for 6-aminocaproic acid, up 101-fold. Furthermore, G418K exhibited an 86-fold enhancement substrate specificity adipic compared acid. Our work provides not only promising biocatalysts nylon monomer biosynthesis but also strategy efficient NRPSs engineering.

Язык: Английский

Combing Directed Enzyme Evolution with Metabolic Engineering to Develop Efficient Microbial Cell Factories DOI Creative Commons

Yuyao Ren,

Ewelina Celińska,

Peng Cai

и другие.

Chem & Bio Engineering, Год журнала: 2025, Номер unknown

Опубликована: Май 1, 2025

Язык: Английский

Процитировано

0
Biocatalytic synthesis of vanillin from biomass-derived compounds：A review DOI
Zhigang Zhang, Shi‐Kai Jiang, Xi Shen

и другие.

Catalysis Today, Год журнала: 2024, Номер 445, С. 115077 - 115077

Опубликована: Сен. 27, 2024

Язык: Английский

Процитировано

2
Computation-driven redesign of an NRPS-like carboxylic acid reductase improves activity and selectivity DOI Creative Commons
Kun Shi, Ju‐Mou Li,

Mu-Qiang Wang

и другие.

Science Advances, Год журнала: 2024, Номер 10(48)

Опубликована: Ноя. 29, 2024

Engineering nonribosomal peptide synthetases (NRPSs) has been a “holy grail” in synthetic biology due to their modular nature and limited understanding of catalytic mechanisms. Here, we reported computational redesign the “gate-keeper” adenylation domain model NRPS-like enzyme carboxylic acid reductases (CARs) by using approximate mechanism-based geometric criteria Rosetta energy score. Notably, Mab CAR3 mutants ACA-1 ACA-4 displayed remarkable improvement efficiency ( k cat / K M ) for 6-aminocaproic acid, up 101-fold. Furthermore, G418K exhibited an 86-fold enhancement substrate specificity adipic compared acid. Our work provides not only promising biocatalysts nylon monomer biosynthesis but also strategy efficient NRPSs engineering.

Язык: Английский

Процитировано

1