7C1L

Crystal structure of the starter condensation domain of rhizomide synthetase RzmA mutant R148A in complex with C8-CoA

7C1L の概要

• エントリーDOI: 10.2210/pdb7c1l/pdb
• 分子名称: Non-ribosomal peptide synthetase modules, OCTANOYL-COENZYME A, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total)
• 機能のキーワード: nonribosomal peptide synthesis, rzma-cs, starter condensation (cs) domains, c8-coa, biosynthetic protein
• 由来する生物種: Paraburkholderia rhizoxinica HKI 454
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 49473.67

構造登録者

Zhong, L.,Diao, X.,Zhang, N.,Li, F.W.,Zhou, H.B.,Chen, H.N.,Ren, X.,Zhang, Y.,Wu, D.,Bian, X. (登録日: 2020-05-05, 公開日: 2020-11-25, 最終更新日: 2023-11-29)

主引用文献

Zhong, L.,Diao, X.,Zhang, N.,Li, F.,Zhou, H.,Chen, H.,Bai, X.,Ren, X.,Zhang, Y.,Wu, D.,Bian, X.
Engineering and elucidation of the lipoinitiation process in nonribosomal peptide biosynthesis.
Nat Commun, 12:296-296, 2021

PubMed Abstract: Nonribosomal peptide synthetases containing starter condensation domains direct the biosynthesis of nonribosomal lipopeptides, which generally exhibit wide bioactivities. The acyl chain has strong impacts on bioactivity and toxicity, but the lack of an in-depth understanding of starter condensation domain-mediated lipoinitiation limits the bioengineering of NRPSs to obtain novel derivatives with desired acyl chains. Here, we show that the acyl chains of the lipopeptides rhizomide, holrhizin, and glidobactin were modified by engineering the starter condensation domain, suggesting a workable approach to change the acyl chain. Based on the structure of the mutated starter condensation domain of rhizomide biosynthetic enzyme RzmA in complex with octanoyl-CoA and related point mutation experiments, we identify a set of residues responsible for the selectivity of substrate acyl chains and extend the acyl chains from acetyl to palmitoyl. Furthermore, we illustrate three possible conformational states of starter condensation domains during the reaction cycle of the lipoinitiation process. Our studies provide further insights into the mechanism of lipoinitiation and the engineering of nonribosomal peptide synthetases.

PubMed: 33436600
DOI: 10.1038/s41467-020-20548-8

実験手法

X-RAY DIFFRACTION (1.85 Å)