2014.07.22【英译中】SCI 连载之九

小妮丫头 (流火) 路人甲
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发表于:2014-07-22 22:53 [只看楼主] [划词开启]

2014.07.22【英译中】SCI 连载之九


Applicability of ribosome engineering to myxobacteria

粘细菌核糖体工程的适用性

Interest in myxobacteria, an important source of novel classes of secondary metabolites, has increased. The genomes of myxobacteria are large (9.14 Mb in Myxococcus Xanthus and 13.03 Mb in Sorangium cellulosum), similar or larger than the genome of S. coelicolor(8.67 Mb). Myxobacterial genomes have been found to encode many genes involved in the synthesis of secondary metabolites (e.g., 8.6 % of the M. Xanthus genome), opening the possibility of discovering clinically relevant natural products (Goldman et al.2006; Schneiker et al.2007; Wenzel and Muller 2009). Of the myxobacteria, the genus Sorangium is particularly valuable, as 46 % of metabolites isolated from myxobacteria are derived from this genus. Most myxobacterial metabolites are polyketides, nonribosomal peptides, and hybrids of the two structures. Hence, activation or enhancement of cryptic genes in the genus Sorangium is of interest, and the strategy of ribosome engineering may be utilized successfully for drug discovery.

粘细菌——一种新的次级代谢产物的重要来源,已经吸引了众科学家的兴趣。粘细菌的基因组很大(Myxococcus Xanthus9.14MbSorangium cellulosum13.03Mb),比S. coelicolor(8.67 Mb)的基因组还大。粘细菌的基因组已经被发现能够编码很多参与次级代谢产物合成的基因(如M. Xanthus中达到8.6 %),开启发现临床有关天然产物的新方法的可能性。粘细菌中的Sorangium属特别值得重视,因为从粘细菌中分离得到的代谢物中有46 %都是来自这个属。大多数粘细菌代谢物都是多聚乙酰,非核糖体肽类,还有两种结构的混合物。因此,Sorangium属中隐藏基因的激活或者强化都十分有趣。核糖体工程的应用对药物发现的策略可能会很成功。

 

Applicability of ribosome engineering to eukaryotes

真核生物核糖体工程的适用性

Fungi have been among the most important sources of biologically active secondary metabolites. Following the publication of the complete genome sequence of the model yeast Saccharomyces cerevisiae(Goffeau et al.1996), hundreds of fungal genome projects have been carried out worldwide. As a result, large numbers of fungal genome sequences are now available publicly, including those of well-known producers of secondary metabolites, such as Aspergillus oryzae and Penicillium chrysogenum(Ma and Fedorova 2010). Their genomes, like those of Streptomyces, are also enriched in genes involved in secondary metabolite biosynthesis. Similar to Streptomyces, however, most biosynthetic gene clusters in fungi are either silent or expressed at very low levels under laboratory conditions. Thus, understanding the physiological conditions under which these genes are activated and developing a pragmatic approach for utilizing such genetic potential is important. A simple and yet efficient approach to isolate more secondary metabolites by exploring the genetic potential in fungi is to vary easily accessible cultivation parameters (Bode et al. 2002). Alternatively, physiological interaction among microorganisms may be practical. For example, cocultivation of Aspergillus nidulans and Streptomyces rapamycinicus selectively stimulated cryptic fungal gene clusters involved in the biosynthesis of secondary metabolites, such as orsellinic acid, lecanoric acid, and the cathepsin K inhibitors F-9775A and F-9775B (Schroeckh et al. 2009). Small molecule epigenetic modifiers, such as the DNA methyltransferase inhibitor 5-azacytidine and the histone deacetylase inhibitor suberoylanilide hydroxamic acid, have been shown effective not only in altering secondary metabolite profiles but in generating new biomolecules (Williams et al.2008). Likewise, nucleoid structure may be playing an analogous role to fungal chromatin structure in controlling transcriptional programs in actinomycetes, thus Moore et al. (2012) reported chemical elicitors that stimulate biosynthetic gene clusters in Streptomyces.

真菌被认为是生物活性次级代谢产物最重要的资源之一。在模式菌株酵母菌Saccharomyces cerevisiae被报道进行了全基因测序后,世界上有许多真菌基因计划已经实现。因此,很多真菌基因序列现在已经共布,包括Aspergillus oryzae Penicillium chrysogenum在内的许多次级代谢产物的有名的生产者。同Streptomyces一样,它们的基因组在次级代谢合成基因中十分的丰富。和Streptomyces类似的是,大部分真菌的合成基因簇在实验室条件下不是保持沉默就是表达结果很弱。因此,理解这些生理条件是被哪些基因激活并且发展一种实用的方法来利用这些基因的潜在能力将十分重要。一种简单然而十分有效地通过探索真菌基因潜在能力来分离更多次级代谢产物的方法,就是改变容易改变的培养参数。或者,利用生理上微生物间的交互作用也可能具有实际意义。例如,对Aspergillus nidulans Streptomyces rapamycinicus进行协同培养能够特异性地刺激餐具次级代谢物合成的潜在的真菌基因簇,例如苔色酸、红粉苔酸、组织蛋白酶K抑制剂F-9775A F-9775B。后形成的修饰小分子化合物,如DNA甲基转移酶抑制剂5-azacytidine和组蛋白脱乙酰基酶抑制剂suberoylanilide hydroxamic acid,已被证实不仅在改变次级代谢物特性方面有影响,在形成新活性分子上也很有作用。同样地,放线菌的核结构应该与真菌的调控转录系统具有类似的结构,因此Moore等人报道了Streptomyces中激发生物合成基因簇的化学的真菌激发子。

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