bryA: an unusual modular polyketide synthase gene from the uncultivated bacterial symbiont of the marine bryozoan Bugula neritina.
"Candidatus Endobugula sertula," the uncultivated bacterial symbiont of Bugula neritina, is the proposed source of the bryostatin family of anticancer compounds. We cloned a large modular polyketide synthase (PKS) gene complex from "Candidatus Endobugula sertula" and characterized one gene, bryA, which we propose is responsible for the initial steps of bryostatin biosynthesis. Typical PKS domains are present. However, acyltransferase domains are lacking in bryA, and beta-ketoacyl synthase domains of bryA cluster with those of PKSs with discrete, rather than integral, acyltransferases. We propose a model for biosynthesis of the bryostatin D-lactate starter unit by the bryA loading module, utilizing atypical domains homologous to FkbH, KR, and DH. The bryA gene product is proposed to synthesize a portion of the pharmacologically active part of bryostatin and may be useful in semisynthesis of clinically useful bryostatin analogs.
Hildebrand
Mark
M
Scripps Institution of Oceanography, Marine Biology Research Division, Center for Marine Biotechnology and Biomedicine and UCSD Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA.
Waggoner
Laura E
LE
Liu
Haibin
H
Sudek
Sebastian
S
Allen
Scott
S
Anderson
Christine
C
Sherman
David H
DH
Haygood
Margo
M
D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism; D001419:Bacteria / Q000201:enzymology*; D001426:Bacterial Proteins / Q000235:genetics; D054713:Bryostatins; D002013:Bryozoa / Q000382:microbiology*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018942:Macrolides / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D048630:Polyketide Synthases / Q000235:genetics* / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D013559:Symbiosis
D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D054713:Bryostatins; D018942:Macrolides; C046785:bryostatin 1; D012313:RNA; D048630:Polyketide Synthases