title: Biosynthesis of macrolactam BE-14106 involves two distinct PKS systems and amino acid processing enzymes for generation of the aminoacyl starter unit.
abstract: BE-14106 is a macrocyclic lactam with an acyl side chain previously identified in a marine-derived Streptomyces sp. The gene cluster for BE-14106 biosynthesis was cloned from a Streptomyces strain newly isolated from marine sediments collected in the Trondheimsfjord (Norway). Bioinformatics and experimental analyses of the genes in the cluster suggested an unusual mechanism for assembly of the molecule. Biosynthesis of the aminoacyl starter apparently involves the concerted action of a distinct polyketide synthase (PKS) system and several enzymes that activate and process an amino acid. The resulting starter unit is loaded onto a second PKS complex, which completes the synthesis of the macrolactam ring. Gene inactivation experiments, enzyme assays with heterologously expressed proteins, and feeding studies supported the proposed model for the biosynthesis and provided new insights into the assembly of macrolactams with acyl side chain.
authors.affiliation: Department of Biotechnology, Norwegian University of Science and Technology, N-7491 Trondheim, Norway.
authors.forename: Hanne
authors.initials: H
authors.lastname: Jørgensen
authors.forename: Kristin F
authors.initials: KF
authors.lastname: Degnes
authors.forename: Håvard
authors.initials: H
authors.lastname: Sletta
authors.forename: Espen
authors.initials: E
authors.lastname: Fjaervik
authors.forename: Alexander
authors.initials: A
authors.lastname: Dikiy
authors.forename: Lars
authors.initials: L
authors.lastname: Herfindal
authors.forename: Per
authors.initials: P
authors.lastname: Bruheim
authors.forename: Geir
authors.initials: G
authors.lastname: Klinkenberg
authors.forename: Harald
authors.initials: H
authors.lastname: Bredholt
authors.forename: Gyrid
authors.initials: G
authors.lastname: Nygård
authors.forename: Stein O
authors.initials: SO
authors.lastname: Døskeland
authors.forename: Trond E
authors.initials: TE
authors.lastname: Ellingsen
authors.forename: Sergey B
authors.initials: SB
authors.lastname: Zotchev
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D007769:Lactams / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D005810:Multigene Family; D048630:Polyketide Synthases / Q000235:genetics / Q000378:metabolism*; D013302:Streptomyces / Q000201:enzymology / Q000235:genetics
chemical_list: D000596:Amino Acids; D007769:Lactams; C076081:BE 14106; D048630:Polyketide Synthases