title: Sparsomycin Biosynthesis Highlights Unusual Module Architecture and Processing Mechanism in Non-ribosomal Peptide Synthetase.
abstract: Sparsomycin is a model protein synthesis inhibitor that blocks peptide bond formation by binding to the large ribosome subunit. It is a unique dipeptidyl alcohol, consisting of a uracil acrylic acid moiety and a monooxo-dithioacetal group. To elucidate the biosynthetic logic of sparsomycin, a biosynthetic gene cluster for sparsomycin was identified from the producer Streptomyces sparsogenes by genome mining, targeted gene mutations, and heterologous expression. Both the genetic and enzymatic studies revealed a minimum set of non-ribosomal peptide synthetases needed for generating the dipeptidyl alcohol scaffold of sparsomycin, featuring unusual mechanisms in dipeptidyl assembly and off-loading.
authors.affiliation: †Department of Chemical and Biomolecular Engineering, University of California, 201 Gilman Hall, MC 1462, Berkeley, California 94720, United States.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Rui
authors.affiliation: †Department of Chemical and Biomolecular Engineering, University of California, 201 Gilman Hall, MC 1462, Berkeley, California 94720, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.forename: Mo
authors.initials: M
authors.lastname: Han
authors.affiliation: ∥Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, Pennsylvania 15260, United States.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Liu
authors.forename: Shuangjun
authors.initials: S
authors.lastname: Lin
authors.affiliation: †Department of Chemical and Biomolecular Engineering, University of California, 201 Gilman Hall, MC 1462, Berkeley, California 94720, United States.|⊥Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D053898:Biosynthetic Pathways; D005810:Multigene Family; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000737:chemistry / Q000378:metabolism*; D013033:Sparsomycin / Q000737:chemistry / Q000378:metabolism*; D013302:Streptomyces / Q000235:genetics / Q000378:metabolism*
chemical_list: D000903:Antibiotics, Antineoplastic; D001426:Bacterial Proteins; D011500:Protein Synthesis Inhibitors; D013033:Sparsomycin; D010453:Peptide Synthases