Polyketide assembly lines of uncultivated sponge  symbionts from structure-based gene targeting.
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.
Fisch
Katja M
KM
Kekulé Institute of Organic Chemistry and Biochemistry, University of Bonn, Bonn, Germany.
Gurgui
Cristian
C
Heycke
Nina
N
van der Sar
Sonia A
SA
Anderson
Sally A
SA
Webb
Victoria L
VL
Taudien
Stefan
S
Platzer
Matthias
M
Rubio
Brent K
BK
Robinson
Sarah J
SJ
Crews
Phillip
P
Piel
Jörn
J
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
D000970:Antineoplastic Agents; D003374:Coumarins; D018942:Macrolides; D011753:Pyrones; C498383:psymberin; D048630:Polyketide Synthases