title: Sequence, cloning, and analysis of the fluvirucin B1 polyketide synthase from Actinomadura vulgaris.
abstract: Fluvirucin B1 , produced by Actinomadura vulgaris, is a 14-membered macrolactam active against a variety of infectious fungi as well as influenza A. Despite considerable interest from the synthetic community, very little information is available regarding the biosynthetic origins of the fluvirucins. Herein, we report the identification and initial characterization of the fluvirucin B1 polyketide synthase and related enzymes. The cluster consists of five extender modules flanked by an N-terminal acyl carrier protein and C-terminal thioesterase domain. All but one of the synthase modules contain the full complement of tailoring domains (ketoreductase, dehydratase, and enoyl reductase) as determined by sequence homology with known polyketide synthases. Acitve site analyses of several key components of the cluster are performed to further verify that this gene cluster is associated with production of fluvirucin B1 . This work will both open doors toward a better understanding of macrolactam formation and provide an avenue to genetics-based diversification of fluvirucin structure.
authors: Department of Chemistry, University of Massachusetts , 710 N. Pleasant Street, Amherst, Massachusetts 01003, United States.
authors: Tsung-Yi
authors: TY
authors: Lin
authors: Lawrence S
authors: LS
authors: Borketey
authors: Gitanjeli
authors: G
authors: Prasad
authors: Stephanie A
authors: SA
authors: Waters
authors: Nathan A
authors: NA
authors: Schnarr
mesh_terms: D000192:Actinomycetales / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D000213:Acyl Carrier Protein / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000235:genetics; D006836:Hydro-Lyases / Q000378:metabolism; D007769:Lactams / Q000378:metabolism; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism; D005810:Multigene Family; D048630:Polyketide Synthases / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D000213:Acyl Carrier Protein; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D007769:Lactams; D009097:Multienzyme Complexes; C000588927:fluvirucin B1; D048630:Polyketide Synthases; D006836:Hydro-Lyases
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