Decoding cyclase-dependent assembly of hapalindole and fischerindole alkaloids
Shasha Li1,2, Andrew N Lowell1, Sean A Newmister1
1Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.
Abstract:
The formation of C-C bonds in an enantioselective fashion to create complex polycyclic scaffolds in the hapalindole- and fischerindole- type alkaloids from Stigonematales cyanobacteria represents a compelling and urgent challenge in adapting microbial biosynthesis as a catalytic platform in drug development. Here we determine the biochemical basis for tri- and tetracyclic core formation in these secondary metabolites, involving a new class of cyclases that catalyze a complex cyclization cascade.
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