Download MendeleyStructural basis for selectivity in a highly reducing type II polyketide synthase.
Du, D., Katsuyama, Y., Horiuchi, M., Fushinobu, S., Chen, A., Davis, T.D., Burkart, M.D., Ohnishi, Y.(2020) Nat Chem Biol 16: 776-782
- PubMed: 32367018
- DOI: https://doi.org/10.1038/s41589-020-0530-0
- Primary Citation of Related Structures:
6KXD, 6KXE, 6KXF - PubMed Abstract:
In type II polyketide synthases (PKSs), the ketosynthase-chain length factor (KS-CLF) complex catalyzes polyketide chain elongation with the acyl carrier protein (ACP). Highly reducing type II PKSs, represented by IgaPKS, produce polyene structures instead of the well-known aromatic skeletons. Here, we report the crystal structures of the Iga11-Iga12 (KS-CLF) heterodimer and the covalently cross-linked Iga10=Iga11-Iga12 (ACP=KS-CLF) tripartite complex. The latter structure revealed the molecular basis of the interaction between Iga10 and Iga11-Iga12, which differs from that between the ACP and KS of Escherichia coli fatty acid synthase. Furthermore, the reaction pocket structure and site-directed mutagenesis revealed that the negative charge of Asp?113 of Iga11 prevents further condensation using a ¦Â-ketoacyl product as a substrate, which distinguishes IgaPKS from typical type II PKSs. This work will facilitate the future rational design of PKSs.
Organizational Affiliation:
Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan.
