Fig. 4: Site-selective biocatalytic and semi-synthetic strategies enabled the late-stage bromination of (−)-premarineosin A (3). | Communications Chemistry

Fig. 4: Site-selective biocatalytic and semi-synthetic strategies enabled the late-stage bromination of (−)-premarineosin A (3).

From: Metabolic engineering and late-stage functionalization expand the chemical space of the antimalarial premarineosin A

Fig. 4: Site-selective biocatalytic and semi-synthetic strategies enabled the late-stage bromination of (−)-premarineosin A (3).

a In silico docking of (−)-premarineosin A (3) (orange) into the AlphaFold-predicted structure of D3 (sage green) with FAD (yellow), showing favorable positioning for electrophilic aromatic substitution at the A-ring pyrrole and displaying proximity to critical residues for catalysis (Lys79). b Scheme of biocatalytic (top) and semi-synthetic (bottom) bromination of (−)-premarineosin A (3) analogs. c HPLC traces of D3 and no enzyme control reactions. The peak corresponding to 1-bromo premarineosin A (11) is only observed post-reaction. d HPLC traces of the NBS reaction. The peak corresponding to 12-bromo premarineosin A (12) is only observed post-reaction.

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