The construction of powerful cell factories requires intensive genetic engineering for the addition of new functionalities and the remodeling of native pathways and processes. The present study demonstrates the feasibility of extensive genome reprogramming using modular, specialized de novo-assembled neochromosomes in yeast. The in vivo assembly of linear and circular neochromosomes, carrying 20 native and 21 heterologous genes, enabled the first de novo production in a microbial cell factory of anthocyanins, plant compounds with a broad range of pharmacological properties. Turned into exclusive expression platforms for heterologous and essential metabolic routes, the neochromosomes mimic native chromosomes regarding mitotic and genetic stability, copy number, harmlessness for the host and editability by CRISPR/Cas9. This study paves the way for future microbial cell factories with modular genomes in which core metabolic networks, localized on satellite, specialized neochromosomes can be swapped for alternative configurations and serve as landing pads for the addition of functionalities.

强大的细胞工厂的建设需要密集的基因工程，以增加新的功能和重塑天然途径和过程。本研究证明了在酵母中使用模块化的、专门的从头组装的新染色体进行广泛基因组重编程的可行性。携带 20 个天然基因和 21 个异源基因的线性和环状新染色体的体内组装，使第一个从头在微生物细胞工厂生产花青素，一种具有广泛药理特性的植物化合物。新染色体变成了异源和必需代谢途径的独家表达平台，在有丝分裂和遗传稳定性、拷贝数、对宿主无害和 CRISPR/Cas9 可编辑性方面模仿天然染色体。这项研究为未来具有模块化基因组的微生物细胞工厂铺平了道路，其中定位在卫星上的核心代谢网络、专门的新染色体可以交换为替代配置，并用作增加功能的着陆台。