bryA:: An unusual modular polyketide synthase gene from the uncultivated bacterial symbiont of the marine bryozoan Bugula neritina

被引:104
作者
Hildebrand, M
Waggoner, LE
Liu, HB
Sudek, S
Allen, S
Anderson, C
Sherman, DH
Haygood, M [1 ]
机构
[1] Univ Calif San Diego, Ctr Marine Biotechnol & Biomed, Scripps Inst Oceanog, Div Marine Biol Res, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA
[3] Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA
[4] Inst Life Sci, Dept Med Chem, Ann Arbor, MI 48109 USA
来源
CHEMISTRY & BIOLOGY | 2004年 / 11卷 / 11期
关键词
D O I
10.1016/j.chembiol.2004.08.018
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1543 / 1552
页数:10
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