Fig. 1: Overview of the proposed biosynthesis of bacterial rubromycin-type polyketides and final pathway products.
From: Enzymatic spiroketal formation via oxidative rearrangement of pentangular polyketides
a Griseorhodin A biosynthetic gene cluster encoding, e.g., the minimal type II polyketide synthase (PKS), cyclases, and tailoring enzymes9. b Initial steps afford a reactive acyl-carrier protein (ACP)-bound poly-β-ketone, which is subsequently cyclized and modified to 3. Compounds 3 and 11 were previously identified in the course of gene deletion experiments (ΔgrhO5 and ΔgrhO6, respectively, encoding flavin-dependent tailoring enzymes investigated in this work) and assigned as putative advanced intermediates10. The conversion of 3 into 4 via 8 and 11 (dashed box) and additional intermediates was elucidated in this work. A ketoreductase (presumably GrhO10) then converts 4 into 13. c Examples of mature rubromycins likely formed from 13.
