title: Decoding cyclase-dependent assembly of hapalindole and fischerindole alkaloids.
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.
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.|Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Shasha
authors.initials: S
authors.lastname: Li
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Lowell
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Sean A
authors.initials: SA
authors.lastname: Newmister
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Fengan
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Chemistry, Colorado State University, Fort Collins, Colorado, USA.|University of Colorado Cancer Center, Aurora, Colorado, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Williams
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan, USA.|Department of Medicinal Chemistry, University of Michigan, Ann Arbor, Michigan, USA.|Department of Chemistry, University of Michigan, Ann Arbor, Michigan, USA.|Department of Microbiology &Immunology, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: David H
authors.initials: DH
authors.lastname: Sherman
mesh_terms: D055162:Biocatalysis; D019755:Carbon-Carbon Lyases / Q000378:metabolism*; D000458:Cyanobacteria / Q000378:metabolism; D003500:Cyclization; D026121:Indole Alkaloids / Q000737:chemistry / Q000378:metabolism*; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*
chemical_list: D026121:Indole Alkaloids; D007211:Indoles; C491991:fischerindole; D019755:Carbon-Carbon Lyases