title: Structural basis of nonribosomal peptide macrocyclization in fungi.
abstract: Nonribosomal peptide synthetases (NRPSs) in fungi biosynthesize important pharmaceutical compounds, including penicillin, cyclosporine and echinocandin. To understand the fungal strategy of forging the macrocyclic peptide linkage, we determined the crystal structures of the terminal condensation-like (CT) domain and the holo thiolation (T)-CTcomplex of Penicillium aethiopicum TqaA. The first, to our knowledge, structural depiction of the terminal module in a fungal NRPS provides a molecular blueprint for generating new macrocyclic peptide natural products.
authors.affiliation: State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
authors.forename: Jinru
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California Los Angeles, 420 Westwood Plaza, Los Angeles, CA 90095, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Liu
authors.affiliation: Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California Los Angeles, 420 Westwood Plaza, Los Angeles, CA 90095, USA.
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Cacho
authors.affiliation: CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, 430071, China.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: National Center for Protein Science Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 333 Haike Road, Shanghai 201210, China.
authors.forename: Wenming
authors.initials: W
authors.lastname: Qin
authors.affiliation: CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, China.|Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, 430071, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Chemical and Biomolecular Engineering, Department of Chemistry and Biochemistry, University of California Los Angeles, 420 Westwood Plaza, Los Angeles, CA 90095, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.|Shanghai Collaborative Innovation Center for Biomanufacturing Technology, 30 Meilong Road, Shanghai 200237, China.
authors.forename: Jiahai
authors.initials: J
authors.lastname: Zhou
mesh_terms: D001688:Biological Products / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D003500:Cyclization; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D010407:Penicillium / Q000201:enzymology*; D010453:Peptide Synthases / Q000737:chemistry* / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D001688:Biological Products; D046911:Macromolecular Substances; D010455:Peptides; D010453:Peptide Synthases; C104385:non-ribosomal peptide synthase