TY - JOUR
T1 - bryA
T2 - An unusual modular polyketide synthase gene from the uncultivated bacterial symbiont of the marine bryozoan Bugula neritina
AU - Hildebrand, Mark
AU - Waggoner, Laura E.
AU - Liu, Haibin
AU - Sudek, Sebastian
AU - Allen, Scott
AU - Anderson, Christine
AU - Sherman, David H.
AU - Haygood, Margo
N1 - Funding Information:
L.E.W. is supported by a Department of Defense Postdoctoral Traineeship Award (DAMD17-00-1-0181). Research support was from the National Institutes of Health (5R01CA079678-03) and the Department of Defense (DAMD17-00-1-0183). We are especially grateful to Carolyn Sheehan for assistance.
PY - 2004/11
Y1 - 2004/11
N2 - "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 β-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.
AB - "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 β-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.
UR - http://www.scopus.com/inward/record.url?scp=8844270242&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=8844270242&partnerID=8YFLogxK
U2 - 10.1016/j.chembiol.2004.08.018
DO - 10.1016/j.chembiol.2004.08.018
M3 - Article
C2 - 15556005
AN - SCOPUS:8844270242
SN - 1074-5521
VL - 11
SP - 1543
EP - 1552
JO - Chemistry and Biology
JF - Chemistry and Biology
IS - 11
ER -