美国俄勒冈卫生与科学大学(Oregon Health & Science University，OHSU)的研究人员在Endobugula sertula细菌身上发现一大群基因，能保护海洋生物苔藓虫(Bugula neritina)的幼虫，不受到掠食者的侵害，这个现象非常令科学家好奇，研究人员后来也发现这些物质具有成为抗癌药的潜力。此研究发表于近期的Journal of Natural Products期刊。
Endobugula sertula这种细菌会与它的宿主，也就是海洋苔藓虫形成共生(symbiont)的状态，它也会分泌一种化学分子bryostatin保护着苔藓虫不被鱼类掠食。许多研究也已证实bryostatin具备干扰许多癌细胞株生长的能力。Haygood教授表示：苔藓虫幼虫的皮肤表面覆盖着bryostatin，甚至于在成虫的部份结构也布满这种化合物，也许bryostatin能帮助他们巩固好领土范围以保护幼虫不受到鱼类的掠食。
而研究人员也发现特别是称为bryostatin 1的这一型化合物，具有抗癌的能力，包括对抗胰脏癌、肾脏癌、血癌、非霍奇金氏症淋巴瘤以及黑色素瘤等。目前bryostatin 1也已进入临床试验的第一期，并佐以其它药物进入临床试验的第二期。然而，问题来了，bryostatins在医药的使用量那么大，但是，却很难在苔藓虫以外的环境培养Endobugula sertula，而在溶液中培养苔藓虫以萃取bryostatin化合物的价格非常昂贵，因此bryostatin的取得是相当困难的。
因此，Haygood与她在Scripps海洋学院以及密西根大学的研究团队一起讨论如何让bryostatins这类的化合物能成为商业化生产。研究人员分析了两种不同种类的苔藓虫(一个是生长在深海中，另一种则生长在较浅层的海中)身上的细菌株，然后从中筛选分离出相关的基因组，透过基因工程的方式诱导其生合成bryostatins的前驱物，目前取得的bryostatins前驱物已超过20种以上，并将这些前驱物称为bryostatin 0。
Haygood表示，下一个步骤就是将来自细菌的基因转移到宿主之中，这样就可以在实验室中让宿主生产bryostatins，过程当中除了会产生bryostatins外，也会产生bryostatins的部分片段，或是生产全新的bryostatins相关化合物。最后希望能够透过工业生产的方式大量制备，以供应未来广大的医药需求。
(资料来源 : Bio.com)
部分英文原文：
Identification of the Putative Bryostatin Polyketide Synthase Gene Cluster from “Candidatus Endobugula sertula”, the Uncultivated Microbial Symbiont of the Marine Bryozoan Bugula neritina
Sebastian Sudek,† Nicole B. Lopanik,‡,§ Laura E. Waggoner,†,§ Mark Hildebrand,† Christine Anderson,† Haibin Liu,‡ Amrish Patel,† David H. Sherman,‡ and Margo G. Haygood*,†
Scripps Institution of Oceanography, Marine Biology Research DiVision, and Center for Marine Biotechnology and Biomedicine, UniVersity of California San Diego, La Jolla, California 92093-0202, and Department of Medicinal Chemistry, Life Sciences Institute, UniVersity of Michigan, Ann Arbor, Michigan 48109-2216 ReceiVed July 21, 2006
The bryostatins are protein kinase C modulators with unique structural features and potential anticancer and neurological activities. These complex polyketides were isolated from the marine bryozoan Bugula neritina, but recent studies indicate that they are produced by the uncultured symbiotic bacterium “Candidatus Endobugula sertula” (“E. sertula”). Here we present the putative biosynthetic genes: five modular polyketide synthase (PKS) genes, a discrete acyltransferase, a â-ketosynthase, a hydroxy-methyl-glutaryl CoA synthase (HMG-CS), and a methyltransferase. The cluster was sequenced in two closely related “E. sertula” strains from different host species. In one strain the gene cluster is contiguous, while in the other strain it is split into two loci, with one locus containing the PKS genes and the other containing the accessory genes. Here, we propose a hypothesis for the biosynthesis of the bryostatins. Thirteen PKS modules form the core macrolactone ring, and the pendent methyl ester groups are added by the HMG-CS gene cassette. The resulting hypothetical compound bryostatin 0 is the common basis for the 20 known bryostatins. As “E. sertula” is to date uncultured, heterologous expression of this biosynthetic gene cluster has the potential of producing the bioactive bryostatins in large enough quantities for development into a pharmaceutical.
英文全文链接：http://pubs.acs.org/cgi-bin/sample.cgi/jnprdf/2007/70/i01/html/np060361d.html
