A Monooxygenase from Boreostereum vibrans Catalyzes Oxidative Decarboxylation in a Divergent Vibralactone Biosynthesis Pathway

Abstract

The oxidative decarboxylation of prenyl 4-hydroxybenzoate to prenylhydroquinone has been frequently proposed for the biosynthesis of prenylated (hydro)quinone derivates (sometimes meroterpenoids), yet no corresponding genes or enzymes have so far been reported. AF AD-binding monooxygenase (VibMO1) was identified that converts prenyl 4hydroxybenzoate into prenylhydroquinone and is likely involved in the biosynthesis of vibralactones and other meroterpenoids in the basidiomycete Boreostereum vibrans. Feeding of 3-allyl-4-hydroxybenzylalcohol, an analogue of the vibralactone pathway intermediate 3-prenyl-4-hydroxybenzylalcohol, generated 20 analogues with different scaffolds.This demonstrated divergent pathwayst os keletally distinct compounds initiating from as ingle precursor,t hus providing the first insight into anovel biosynthetic pathway for 3-substituted g-butyrolactones from ashikimate origin.

Biochemical and structural basis for a flavin-monooxygenase catalyzing oxepinone formation and the complete biosynthesis of vibralactone

“…Vibralactone has a dimethylallyl group and its bicyclic lactone core can be derived from 2, thus we hypothesized that the vibralactone biosynthesis may begin with prenylation of 2 to give 3-prenyl 4-hydroxybenzoate (4), which may undergo stepwise reductions via 3-prenyl-4-hydroxybenzaldehyde (5) to the alcohol 6. To test the hypothesis, we conducted the intermediate analogue feeding as used in our prior studies 15 . Compounds 4a and 5a (Fig.…”

“…Vibralactone has a unique chemical structure and potent biological activity, which make vibralactone a worthy target for biosynthetic investigation. Based on initial incorporation studies with [U- 13 C]4hydroxybenzoate and analogue intermediate feedings to the B. vibrans growing culture, we established that (i) the bicyclic lactone core of vibralactone (1) is derived from an aryl ring and 4-hydroxybenzoate (2) serves as the direct ring precursor of vibralactone 14 ; (ii) 3-prenyl-4-hydroxybenzylalcohol ( 6) is an onpathway biosynthetic intermediate leading to 1,5-seco-vibralactone (3) and vibralactone (1) 15 . Furthermore, we revealed the enzymatic and structural basis for the last step of cyclization of 3 to 1, which is catalyzed by an unprecedent cyclase VibC 16 .…”

Synthesis and Biological Evaluation of Analogues of Butyrolactone I as PTP1B Inhibitors

“…p -Hydroxybenzaldehyde ( 1a ) generated phenol oxide anions under potassium hydroxide (KOH), which reacted with chloroisoprene to form intermediate 1b via Friedel–Crafts alkylation [ 38 , 39 ]. Under 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), 1b was refluxed in toluene to form the pyran ring to obtain 1c [ 40 ]. Moreover, 1b was protected by tetrahydropyran (THP) and benzyl to obtain 1d and 1e, respectively [ 41 , 42 ].…”

Allylphenols as a new class of human 15‐lipoxygenase‐1 inhibitors

“…2,6‐diallyl‐4‐(hydroxymethyl)phenol was prepared by reduction of 44 with sodium borohydride as previously reported (Yang et al, 2016). A solution of 44 (40 mmol) in cooled methanol (50 ml) was treated with sodium borohydride (2.3 g, 60 mmol) at 0°C during 2 hr.…”