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Keywords:

  • cyclases;
  • engineered biosynthesis;
  • monooxygenases;
  • multienzyme complexes;
  • polyketides
Thumbnail image of graphical abstract

Synergistic tailoring: Formation of the pentangular aglycon of pradimicin A requires the synergistic actions of the monooxygenase PdmH, which hydroxylates ring B, and the two cyclases PdmK and PdmL. Removal of any one of three enzymes resulted in the biosynthesis of shunt products that are not properly oxidized and cyclized. The concerted actions of the enzymes may serve as a mechanism to suppress spontaneous cyclization of the extended dodecaketide backbone.