Extended Data Fig. 9: Catalytic mechanism of polyketoacyl-CoA thiolase (PKT) and representative PKS III 2-PS. | Nature Catalysis

Extended Data Fig. 9: Catalytic mechanism of polyketoacyl-CoA thiolase (PKT) and representative PKS III 2-PS.

From: A polyketoacyl-CoA thiolase-dependent pathway for the synthesis of polyketide backbones

Extended Data Fig. 9

Cys/His/Cys is the catalytic triad of PKT activity, enabling a two-step, ping-pong mechanism for the thiolytic condensation reaction using substrates with multiple keto-groups (for example acetoacetyl-CoA). Notably, this catalytic mechanism is distinct from that of PKS III, where the core catalytic triad is Cys/His/Asn, with Asn (asparagine) playing a critical role in catalysing malonyl-CoA decarboxylation and stabilizing the condensation transition state.

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