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Publication Abstract from PubMed

Modular type I polyketide synthases (PKSs) are versatile biosynthetic systems that initiate, successively elongate, and modify acyl chains. Intermediate transfer between modules is mediated via docking domains, which are attractive targets for PKS pathway engineering to produce natural product analogs. We identified a class 2 docking domain in cyanobacterial PKSs and determined crystal structures for two docking domain pairs, revealing a distinct class 2 docking strategy for promoting intermediate transfer. The selectivity of class 2 docking interactions, demonstrated in binding and biochemical assays, could be altered by mutagenesis. We determined the ideal fusion location for exchanging class 1 and class 2 docking domains and demonstrated effective polyketide chain transfer in heterologous modules. Thus, class 2 docking domains are tools for rational bioengineering of a broad range of PKSs containing either class 1 or 2 docking domains.

Cyanobacterial polyketide synthase docking domains: a tool for engineering natural product biosynthesis.,Whicher JR, Smaga SS, Hansen DA, Brown WC, Gerwick WH, Sherman DH, Smith JL Chem Biol. 2013 Nov 21;20(11):1340-51. doi: 10.1016/j.chembiol.2013.09.015. Epub , 2013 Oct 31. PMID:24183970^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.