Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias, Universidad de Oviedo, 33006 Oviedo, Spain.
Arch Microbiol. 2012 Jun;194(6):549-55. doi: 10.1007/s00203-011-0781-y. Epub 2011 Dec 27.
In silico database searches allowed the identification in the S. flavogriseus ATCC 33331 genome of a carbapenem gene cluster highly related to the S. cattleya thienamycin one. This is the second cluster found for a complex highly substituted carbapenem. Comparative analysis revealed that both gene clusters display a high degree of synteny in gene organization and in protein conservation. Although the cluster appears to be silent under our laboratory conditions, the putative metabolic product was predicted from bioinformatics analyses using sequence comparison tools. These data, together with previous reports concerning epithienamycins production by S. flavogriseus strains, suggest that the cluster metabolic product might be a thienamycin-like carbapenem, possibly the epimeric epithienamycin. This finding might help in understanding the biosynthetic pathway to thienamycin and other highly substituted carbapenems. It also provides another example of genome mining in Streptomyces sequenced genomes as a powerful approach for novel antibiotic discovery.
通过计算机数据库搜索，在 S. flavogriseus ATCC 33331 基因组中鉴定出一个碳青霉烯基因簇，该基因簇与 S. cattleya 噻霉素基因簇高度相关。这是第二个被发现的复杂的高度取代的碳青霉烯基因簇。比较分析表明，两个基因簇在基因组织和蛋白质保守性方面具有高度的同线性。尽管该基因簇在我们的实验室条件下似乎处于沉默状态，但根据序列比较工具的生物信息学分析，预测了其可能的代谢产物。这些数据，加上之前关于 S. flavogriseus 菌株产生 epithienamycins 的报道，表明该基因簇的代谢产物可能是一种噻霉素样碳青霉烯，可能是差向异构体 epithienamycin。这一发现可能有助于理解噻霉素和其他高度取代的碳青霉烯的生物合成途径。它还提供了另一个通过对已测序的链霉菌基因组进行基因组挖掘来发现新型抗生素的例子，这是一种强大的方法。
