title: Genetic Organization of Anabaenopeptin and Spumigin Biosynthetic Gene Clusters in the Cyanobacterium Sphaerospermopsis torques-reginae ITEP-024.
abstract: Cyanobacteria produce a broad range of natural products, many of which are potent protease inhibitors. Biosynthetic gene clusters encoding the production of novel protease inhibitors belonging to the spumigin and anabaenopeptin family of nonribosomal peptides were identified in the genome of the bloom-forming cyanobacterium Sphaerospermopsis torques-reginae ITEP-024. The genetic architecture and gene organization of both nonribosomal peptide biosynthetic clusters were compared in parallel with their chemical structure variations obtained by liquid chromatography (LC-MS/MS). The spumigin (spu) and anabaenopeptin (apt) gene clusters are colocated in the genomes of S. torques-reginae ITEP-024 and Nodularia spumigena CCY9414 and separated by a 12 kb region containing genes encoding a patatin-like phospholipase, l-homophenylalanine (l-Hph) biosynthetic enzymes, and four hypothetical proteins. hphABCD gene cluster encoding the production of l-Hph was linked to all eight apt gene clusters investigated here. We suggest that while the HphABCD enzymes are an integral part of the anabaenopeptin biosynthetic pathway, they provide substrates for the biosynthesis of both anabaenopeptins and spumigins. The organization of the spu and apt suggests a plausible model for the biosynthesis of the 4-(4-hydroxyphenyl)-2-acid (Hpoba) precursor of spumigin variants in S. torques-reginae ITEP-024 based on the acceptable substrates of HphABCD enzymes.
authors.affiliation: University of São Paulo , Center for Nuclear Energy in Agriculture, Piracicaba-SP, Brazil.
authors.forename: Stella T
authors.identifier: 0000-0002-1703-5627
authors.initials: ST
authors.lastname: Lima
authors.affiliation: University of São Paulo , Center for Nuclear Energy in Agriculture, Piracicaba-SP, Brazil.
authors.forename: Danillo O
authors.identifier: 0000-0002-3666-2220
authors.initials: DO
authors.lastname: Alvarenga
authors.affiliation: Pontifical Catholic University of Campinas , Faculty of Chemistry, Campinas-SP, Brazil.
authors.forename: Augusto
authors.identifier: 0000-0002-0483-0373
authors.initials: A
authors.lastname: Etchegaray
authors.affiliation: University of Helsinki , Department of Food and Environmental Sciences, Division of Microbiology and Biotechnology, Helsinki, Finland.
authors.forename: David P
authors.identifier: 0000-0003-3978-4845
authors.initials: DP
authors.lastname: Fewer
authors.affiliation: University of Helsinki , Department of Food and Environmental Sciences, Division of Microbiology and Biotechnology, Helsinki, Finland.
authors.forename: Jouni
authors.identifier: 0000-0001-5096-3575
authors.initials: J
authors.lastname: Jokela
authors.affiliation: São Paulo State University , College of Agricultural and Veterinary Sciences, Department of Technology, Jaboticabal-SP, Brazil.
authors.forename: Alessandro M
authors.identifier: 0000-0002-8876-3269
authors.initials: AM
authors.lastname: Varani
authors.affiliation: University of São Paulo , School of Pharmaceutical Sciences, São Paulo-SP, Brazil.
authors.forename: Miriam
authors.identifier: 0000-0003-3586-1268
authors.initials: M
authors.lastname: Sanz
authors.affiliation: University of São Paulo , School of Pharmaceutical Sciences, São Paulo-SP, Brazil.
authors.forename: Felipe A
authors.identifier: 0000-0003-4207-4908
authors.initials: FA
authors.lastname: Dörr
authors.affiliation: University of São Paulo , School of Pharmaceutical Sciences, São Paulo-SP, Brazil.
authors.forename: Ernani
authors.identifier: 0000-0001-7614-3014
authors.initials: E
authors.lastname: Pinto
authors.affiliation: University of Helsinki , Department of Food and Environmental Sciences, Division of Microbiology and Biotechnology, Helsinki, Finland.
authors.forename: Kaarina
authors.identifier: 0000-0002-2904-0458
authors.initials: K
authors.lastname: Sivonen
authors.affiliation: University of São Paulo , Center for Nuclear Energy in Agriculture, Piracicaba-SP, Brazil.
authors.forename: Marli F
authors.identifier: 0000-0003-2555-7967
authors.initials: MF
authors.lastname: Fiore
mesh_terms: D000458:Cyanobacteria / Q000235:genetics / Q000378:metabolism*; D005810:Multigene Family; D009842:Oligopeptides / Q000096:biosynthesis*; D010456:Peptides, Cyclic / Q000737:chemistry*; D010802:Phylogeny
chemical_list: D009842:Oligopeptides; D010456:Peptides, Cyclic; C577137:spumigin A