Polyketides are a pharmalogically important class of natural products biosynthetically produced by polyketide synthases (PKSs). Type I, or modular PKSs function via sequential catalytic sites organized into modules responsible for a single ketide unit elongation of the growing polyketide chain. Incorporation of specific molecular properties is controlled at the module level. Introduction of structural and functional diversity in polyketides may be realized given an effective modular rearrangement strategy. This requires specific knowledge of assembly processes that control recognition between proteins. As modular interfaces consist of acyl carrier protein (ACP) and ketosynthase (KS) domains, alteration of specificity at these sites should prove critical to harnessing true combinatorial potential of modular PKSs. As no direct structural information s available for these systems, comparison to well-characterized, analogous domains from other sources provides insight into possible recognition interfaces. Appropriate amino acid substitutions should result kinetically competent heterologous ACP/KS pairs. The impact of the proposed mutations on communication between modified ACP and other relevant domains will also be addressed. ? ?
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