title: Polyketide assembly lines of uncultivated sponge  symbionts from structure-based gene targeting.
abstract: There is increasing evidence that uncultivated bacterial symbionts are the true producers of numerous bioactive compounds isolated from marine sponges. The localization and heterologous expression of biosynthetic genes could clarify this issue and provide sustainable supplies for a wide range of pharmaceuticals. However, identification of genes in the usually highly complex symbiont communities remains a challenging task. For polyketides, one of the most important groups of sponge-derived drug candidates, we have developed a general strategy that allows one to rapidly access biosynthetic gene clusters based on chemical moieties. Using this method, we targeted polyketide synthase genes from two different sponge metagenomes. We have obtained from a sponge-bacterial association a complete pathway for the rare and potent antitumor agent psymberin from Psammocinia aff. bulbosa. The data support the symbiont hypothesis and provide insights into natural product evolution in previously inaccessible bacteria.
authors.affiliation: Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Bonn, Germany.
authors.forename: Katja M
authors.initials: KM
authors.lastname: Fisch
authors.forename: Cristian
authors.initials: C
authors.lastname: Gurgui
authors.forename: Nina
authors.initials: N
authors.lastname: Heycke
authors.forename: Sonia A
authors.initials: SA
authors.lastname: van der Sar
authors.forename: Sally A
authors.initials: SA
authors.lastname: Anderson
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Webb
authors.forename: Stefan
authors.initials: S
authors.lastname: Taudien
authors.forename: Matthias
authors.initials: M
authors.lastname: Platzer
authors.forename: Brent K
authors.initials: BK
authors.lastname: Rubio
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Robinson
authors.forename: Phillip
authors.initials: P
authors.lastname: Crews
authors.forename: Jörn
authors.initials: J
authors.lastname: Piel
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry; D003374:Coumarins; D018390:Gene Targeting; D018942:Macrolides / Q000737:chemistry; D054892:Metagenome; D008969:Molecular Sequence Data; D015394:Molecular Structure; D005810:Multigene Family; D048630:Polyketide Synthases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011161:Porifera / Q000201:enzymology / Q000235:genetics / Q000382:microbiology*; D011753:Pyrones / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013559:Symbiosis
chemical_list: D000970:Antineoplastic Agents; D003374:Coumarins; D018942:Macrolides; D011753:Pyrones; C498383:psymberin; D048630:Polyketide Synthases