BACKGROUND Large-scale genome reduction has been performed to significantly improve the performance of microbial chassis. Identification of the essential or dispensable genes is pivotal for genome reduction to avoid synthetic lethality. Here, taking Streptomyces as an example, we developed a combinatorial strategy for systematic identification of large and dispensable genomic regions in Streptomyces based on multi-omics approaches. RESULTS Phylogenetic tree analysis revealed that the model strains including S. coelicolor A3(2), S. albus J1074 and S. avermitilis MA-4680 were preferred reference for comparative analysis of candidate genomes. Multiple genome alignment suggested that the Streptomyces genomes embodied highly conserved core region and variable sub-telomeric regions, and may present symmetric or asymmetric structure. Pan-genome and functional genome analyses showed that most conserved genes responsible for the fundamental functions of cell viability were concentrated in the core region and the vast majority of abundant genes were dispersed in the sub-telomeric regions. These results suggested that large-scale deletion can be performed in sub-telomeric regions to greatly streamline the Streptomyces genomes for developing versatile chassis. CONCLUSIONS The integrative approach of comparative genomics, functional genomics and pan-genomics can not only be applied to perform a multi-tiered dissection for Streptomyces genomes, but also work as a universal method for systematic analysis of removable regions in other microbial hosts in order to generate more miscellaneous and versatile chassis with minimized genome for drug discovery.

中文翻译：

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基于比较分析方法的链霉菌中可分配基因组区域的全面解剖。

背景技术已经进行了大规模的基因组减少以显着改善微生物底盘的性能。鉴定必需或可有可无的基因对于减少基因组以避免合成杀伤力至关重要。在这里，以链霉菌为例，我们开发了一种组合策略，用于基于多组学方法系统地鉴定链霉菌中较大且可分配的基因组区域。结果系统树分析表明，模型菌株包括coelicolor A3（2），albus J1074和averaveris MA-4680是比较候选基因组的首选参考。多个基因组比对表明，链霉菌基因组体现了高度保守的核心区域和可变的亚端粒区域，并可能呈现对称或不对称的结构。泛基因组和功能基因组分析表明，负责细胞生存的基本功能的大多数保守基因都集中在核心区域，绝大多数丰富基因分散在亚端粒区域。这些结果表明，可以在亚端粒区域进行大规模缺失，以极大地简化链霉菌基因组，以开发通用的底盘。结论比较基因组学，功能基因组学和泛基因组学的整合方法不仅可以应用于链霉菌基因组的多层解剖，而且还可以作为一种通用方法对其他微生物宿主中的可移动区域进行系统分析，从而用最小的基因组生成更多杂种和多功能底盘，以进行药物发现。