6IYT

Crystal Structure of the acyltransferase domain from second module 14 of salinomycin polyketide synthase

Summary for 6IYT

• Entry DOI: 10.2210/pdb6iyt/pdb
• Descriptor: Type I modular polyketide synthase (2 entities in total)
• Functional Keywords: acyltransferase, ethylhmalonyl-coenzyme a, polyketide, transferase
• Biological source: Streptomyces albus subsp. albus
• Total number of polymer chains: 2
• Total formula weight: 97579.02

Authors

Zhang, F.,Zheng, J. (deposition date: 2018-12-17, release date: 2019-07-03, Last modification date: 2023-11-22)

Primary citation

Zhang, F.,Shi, T.,Ji, H.,Ali, I.,Huang, S.,Deng, Z.,Min, Q.,Bai, L.,Zhao, Y.,Zheng, J.
Structural Insights into the Substrate Specificity of Acyltransferases from Salinomycin Polyketide Synthase.
Biochemistry, 58:2978-2986, 2019

PubMed Abstract: Salinomycin with antibacterial and anticoccidial activities is a commercial polyether polyketide widely used in animal husbandry as a food additive. Malonyl-CoA (MCoA), methylmalonyl-CoA (MMCoA), and ethylmalonyl-CoA (EMCoA) are used as extension units in its biosynthesis. To understand how the salinomycin modular polyketide synthase (PKS) strictly discriminates among these extension units, the acyltransferase (AT) domains selecting MCoA, MMCoA, and EMCoA were structurally characterized. Molecular dynamics simulations of the AT structures helped to reveal the key interactions involved in enzyme-substrate recognitions, which enabled the engineering of AT mutants with switched specificity. The catalytic efficiencies ( k/ K) of these AT mutants are comparable with those of the wild-type AT domains. These results set the stage for engineering the AT substrate specificity of modular PKSs.

PubMed: 31199122
DOI: 10.1021/acs.biochem.9b00305

Experimental method

X-RAY DIFFRACTION (1.78 Å)