title: Comparative analysis of the biosynthetic systems for fungal bicyclo[2.2.2]diazaoctane indole alkaloids: the (+)/(-)-notoamide, paraherquamide and malbrancheamide pathways.
abstract: The biosynthesis of fungal bicyclo[2.2.2]diazaoctane indole alkaloids with a wide spectrum of biological activities have attracted increasing interest. Their intriguing mode of assembly has long been proposed to feature a non-ribosomal peptide synthetase, a presumed intramolecular Diels-Alderase, a variant number of prenyltransferases, and a series of oxidases responsible for the diverse tailoring modifications of their cyclodipeptide-based structural core. Until recently, the details of these biosynthetic pathways have remained largely unknown due to lack of information on the fungal derived biosynthetic gene clusters. Herein, we report a comparative analysis of four natural product metabolic systems of a select group of bicyclo[2.2.2]diazaoctane indole alkaloids including (+)/(-)-notoamide, paraherquamide and malbrancheamide, in which we propose an enzyme for each step in the biosynthetic pathway based on deep annotation and on-going biochemical studies.
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors.forename: Shengying
authors.initials: S
authors.lastname: Li
authors.forename: Krithika
authors.initials: K
authors.lastname: Anand
authors.forename: Hong
authors.initials: H
authors.lastname: Tran
authors.forename: Fengan
authors.initials: F
authors.lastname: Yu
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Finefield
authors.forename: James D
authors.initials: JD
authors.lastname: Sunderhaus
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: McAfoos
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tsukamoto
authors.forename: Robert M
authors.initials: RM
authors.lastname: Williams
authors.forename: David H
authors.initials: DH
authors.lastname: Sherman