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PKSs use acyl-CoA derivatives as building blocks for synthesizing complex and functionally diverse polyketides. The loading module of PKSs can often contain a ketosynthase-like (KSq) domain, which if present, loads dicarboxylic acids wherein one of the acid groups has been acylated by CoA (e.g., malonyl-CoA). If this KSq domain is absent, however, then PKSs load monocarboxylic acids wherein the single acid group has already been acylated by CoA (e.g., propionyl-CoA or acetyl-CoA). Meanwhile, the ketosynthase (KS) domains in downstream extension modules use only CoA-acylated dicarboxylic acids as extension units. By considering a large and customizable set of acyl-CoA derivatives as starter and extender units within these constraints, RetroTide can build polyketide products that are as structurally similar to the final target product as possible.
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