Chemoenzymatic synthesis of β-carboline derivatives using McbA, a new ATP-dependent amide synthetase

McbA was characterized in vitro as a novel amide synthetase in the marinacarbolines A–D biosynthetic pathway, catalyzing amide bond formation between 1-acetyl-3-carboxy-β-carboline (1a) and substituted-β-phenethylamines (1b, 2b, 3b) and tryptamine (4b) in an ATP-dependent manner. Enzyme kinetic analyses highlight β-phenethylamine as the most suitable amine donor. McbA showed broad substrate compatibility with substituted amines; 10 new β-carboline analogues were chemoenzymatically generated.