Discovery and heterologous biosynthesis of glycosylated polyketide luteodienoside A reveals unprecedented glucinol-mediated product offloading by a fungal carnitine -acyltransferase domain.

Luteodienoside A is a novel glycosylated polyketide produced by the Australian fungus MST-FP2246, consisting of an unusual 1--β-d-glucopyranosyl--inositol (glucinol) ester of 3-hydroxy-2,2,4-trimethylocta-4,6-dienoic acid. Mining the genome of identified a putative gene cluster for luteodienoside A biosynthesis (), harbouring a highly reducing polyketide synthase (HR-PKS, LtbA) fused at its C-terminus to a carnitine -acyltransferase (cAT) domain. Heterologous pathway reconstitution in , substrate feeding assays and gene truncation confirmed the identity of the cluster and demonstrated that the cAT domain is essential for offloading luteodienoside A from the upstream HR-PKS.