Covering: 1999 up to 2021

Fungal polyketides encompass a range of structurally diverse molecules with a wide variety of biological activities. The giant multifunctional enzymes that synthesize polyketide backbones remain enigmatic, as do many of the tailoring enzymes involved in functional modifications. Recent advances in elucidating biosynthetic gene clusters (BGCs) have revealed numerous examples of fungal polyketide synthases that require the action of collaborating enzymes to synthesize the carbon backbone. This review will discuss collaborating and trans-acting enzymes involved in loading, extending, and releasing polyketide intermediates from fungal polyketide synthases, and additional modifications introduced by trans-acting enzymes demonstrating the complexity encountered when investigating natural product biosynthesis in fungi.