title: Mode of action and biosynthesis of the azabicycle-containing natural products azinomycin and ficellomycin.
abstract: Only a handful of aziridine-containing natural products have been identified out of the more than 100,000 natural products characterized to date. Among this class of compounds, only the azinomycins (azinomycin A and B) and ficellomycin contain an unusual 1-azabicyclo[3.1.0]hexane ring system, which has been reported to be the reason for theDNAcrosslinking abilities and cytotoxicity of these metabolites. Both families of natural products are produced by Streptomyces species, Streptomyces sahachiroi and Streptomyces ficellus, respectively. Up until recently, much of the work on these molecules has focused on the synthesis of these natural products or their corresponding analogs for in vitro investigations evaluating their DNA selectivity. While one of the most intriguing aspects of these natural products is their biosynthesis, progress made in this area was largely impeded by difficulties with obtaining a reliable culture method and securing a consistent source of these natural products. In this review, we will cover the discovery and biological activity of the azinomycins, their mode of action, related synthetic analogs and biosynthesis, and finish with a discussion on the less studied metabolite, ficellomycin.
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, TX 77843, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Foulke-Abel
authors.forename: Hillary
authors.initials: H
authors.lastname: Agbo
authors.forename: Huitu
authors.initials: H
authors.lastname: Zhang
authors.forename: Shogo
authors.initials: S
authors.lastname: Mori
authors.forename: Coran M H
authors.initials: CM
authors.lastname: Watanabe
mesh_terms: D053961:Azabicyclo Compounds; D001688:Biological Products / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004151:Dipeptides; D006020:Glycopeptides / Q000737:chemistry / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D053961:Azabicyclo Compounds; D001688:Biological Products; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004151:Dipeptides; D006020:Glycopeptides; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C051054:azinomycin A; C013532:ficellomycin; D004247:DNA