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Control of Stereoselectivity in Diverse Hapalindole Metabolites is Mediated by Cofactor-Induced Combinatorial Pairing of Stig Cyclases |
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| Authors: | Dr. Shasha Li Dr. Sean A. Newmister Dr. Andrew N. Lowell Dr. Jiachen Zi Callie R. Chappell Dr. Fengan Yu Robert M. Hohlman Prof. Jimmy Orjala Prof. Robert M. Williams Prof. David H. Sherman |
| Affiliation: | 1. Life Sciences Institute, Department of Medicinal Chemistry, The University of Michigan, USA;2. Life Science Institute, The University of Michigan, USA;3. Life Science Institute, The University of Michigan, USA Department of Chemistry, Virginia Tech, Blacksburg, VA, 24061 USA;4. Department of Pharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, 60612 USA;5. Department of Molecular, Cellular & Developmental Biology, The University of Michigan, USA;6. Department of Chemistry, Colorado State University, Fort Collins, CO, 80523 USA University of Colorado Cancer Center, Aurora, CO, 80045 USA;7. Life Sciences Institute, Departments of Medicinal Chemistry, Chemistry, Microbiology & Immunology, The University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI, 48109-2216n USA |
| Abstract: | Stereospecific polycyclic core formation of hapalindoles and fischerindoles is controlled by Stig cyclases through a three-step cascade involving Cope rearrangement, 6-exo-trig cyclization, and a final electrophilic aromatic substitution. Reported here is a comprehensive study of all currently annotated Stig cyclases, revealing that these proteins can assemble into heteromeric complexes, induced by Ca2+, to cooperatively control the stereochemistry of hapalindole natural products. |
| Keywords: | Biokatalyse Cyclasen Indole Oligomerisierung Umlagerungen |