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Structural and Biochemical Analysis of Protein-Protein Interactions Between the Acyl-Carrier Protein and Product Template Domain.


ABSTRACT: In fungal non-reducing polyketide synthases (NR-PKS) the acyl-carrier protein (ACP) carries the growing polyketide intermediate through iterative rounds of elongation, cyclization and product release. This process occurs through a controlled, yet enigmatic coordination of the ACP with its partner enzymes. The transient nature of ACP interactions with these catalytic domains imposes a major obstacle for investigation of the influence of protein-protein interactions on polyketide product outcome. To further our understanding about how the ACP interacts with the product template (PT) domain that catalyzes polyketide cyclization, we developed the first mechanism-based crosslinkers for NR-PKSs. Through in?vitro assays, in?silico docking and bioinformatics, ACP residues involved in ACP-PT recognition were identified. We used this information to improve ACP compatibility with non-cognate PT domains, which resulted in the first gain-of-function ACP with improved interactions with its partner enzymes. This advance will aid in future combinatorial biosynthesis of new polyketides.

SUBMITTER: Barajas JF 

PROVIDER: S-EPMC5161458 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Structural and Biochemical Analysis of Protein-Protein Interactions Between the Acyl-Carrier Protein and Product Template Domain.

Barajas Jesus F JF   Finzel Kara K   Valentic Timothy R TR   Shakya Gaurav G   Gamarra Nathan N   Martinez Delsy D   Meier Jordan L JL   Vagstad Anna L AL   Newman Adam G AG   Townsend Craig A CA   Burkart Michael D MD   Tsai Shiou-Chuan SC  

Angewandte Chemie (International ed. in English) 20161001 42


In fungal non-reducing polyketide synthases (NR-PKS) the acyl-carrier protein (ACP) carries the growing polyketide intermediate through iterative rounds of elongation, cyclization and product release. This process occurs through a controlled, yet enigmatic coordination of the ACP with its partner enzymes. The transient nature of ACP interactions with these catalytic domains imposes a major obstacle for investigation of the influence of protein-protein interactions on polyketide product outcome.  ...[more]

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