Fig. 5: Proposed mechanism for β-O-malonylation and δ-lactonisation by FosTE. | Nature Communications

Fig. 5: Proposed mechanism for β-O-malonylation and δ-lactonisation by FosTE.

From: Covalent warhead assembly in fostriecin biosynthesis involves malonylation-lactonisation by a bifunctional thioesterase and enzymatic demalonylation

Fig. 5: Proposed mechanism for β-O-malonylation and δ-lactonisation by FosTE.

a Proposed mechanism for β-O-malonylation prior to δ-lactonisation. Self-malonylation of catalytic S159 with malonyl-CoA is followed by malonyl transfer onto the C-3 hydroxyl group of the polyketide intermediate. The ACP-bound polyketide is transacylated onto the catalytic S159 of the TE for subsequent cyclisation and off-loading. b Proposed mechanism for β-O-malonylation of released δ-lactone. ACP-bound polyketide is transacylated onto catalytic S159 of the TE for subsequent δ-lactonisation. The malonyl moiety is then transacylated from malonyl-CoA onto S159 and transferred onto the C-3 hydroxyl group of the δ-lactone. c Reaction scheme and EICs for the in vitro reactions of oxoester 31 with FosMod8, FosTE, FosMod8(S159A), FosMod8(R198L/R227L), FosAT8, FosKS8-AT8-KR8, the no-enzyme control reaction and the substrate (31) (left). Reaction scheme and EICs for the in vitro reactions of lactone 25 with FosMod8, FosTE, FosMod8(S159A), FosMod8(R198L/R227L), a negative control, and the product reference 27 (right). Supplementary Figs. 44, 45, 52, 53 for HRMS(/MS) data.

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