<p>The stereospecific polycyclic core formation of hapalindoles and fischerindoles is controlled by the Stig cyclases through a three-step cascade involving Cope rearrangement, 6-<i>exo</i>-trig cyclization and a final electrophilic aromatic substitution. Here we report a comprehensive study of all currently annotated Stig cyclases, and reveal that these proteins can assemble into heteromeric complexes induced by Ca<sup>2+</sup> to cooperatively control the stereochemistry of hapalindole natural products.</p>
<p>The stereospecific polycyclic core formation of hapalindoles and fischerindoles is controlled by the Stig cyclases through a three-step cascade involving Cope rearrangement, 6-<i>exo</i>-trig cyclization and a final electrophilic aromatic substitution. Here we report a comprehensive study of all currently annotated Stig cyclases, and reveal that these proteins can assemble into heteromeric complexes induced by Ca<sup>2+</sup> to cooperatively control the stereochemistry of hapalindole natural products.</p>
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