The methylotrophic yeast Pichia pastoris is firmly established as a host for the production of recombinant proteins, frequently outperforming other heterologous hosts. Already, a sizeable amount of systems biology knowledge has been acquired for this non-conventional yeast. By applying various omics-technologies, productivity features have been thoroughly analyzed and optimized via genetic engineering. However, challenging clonal variability, limited vector repertoire and insufficient genome annotation have hampered further developments. Yet, in the last few years a reinvigorated effort to establish P. pastoris as a host for both protein and metabolite production is visible. A variety of compounds from terpenoids to polyketides have been synthesized, often exceeding the productivity of other microbial systems. The clonal variability was systematically investigated and strategies formulated to circumvent untargeted events, thereby streamlining the screening procedure. Promoters with novel regulatory properties were discovered or engineered from existing ones. The genetic tractability was increased via the transfer of popular manipulation and assembly techniques, as well as the creation of new ones. A second generation of sequencing projects culminated in the creation of the second best functionally annotated yeast genome. In combination with landmark physiological insights and increased output of omics-data, a good basis for the creation of refined genome-scale metabolic models was created. The first application of model-based metabolic engineering in P. pastoris showcased the potential of this approach. Recent efforts to establish yeast peroxisomes for compartmentalized metabolite synthesis appear to fit ideally with the well-studied high capacity peroxisomal machinery of P. pastoris. Here, these recent developments are collected and reviewed with the aim of supporting the establishment of systems metabolic engineering in P. pastoris.

甲基营养酵母巴斯德毕赤酵母已被牢固地确立为生产重组蛋白的宿主，其性能通常优于其他异源宿主。对于这种非常规酵母，已经获得了大量的系统生物学知识。通过应用各种组学技术，已经通过基因工程对生产力特征进行了全面分析和优化。然而，具有挑战性的克隆变异性，有限的载体组成和不足的基因组注释阻碍了进一步的发展。然而，在过去的几年中，为建立P进行了重新的努力。巴斯德作为蛋白质和代谢产物生产的宿主是可见的。已经合成了从萜类化合物到聚酮化合物的各种化合物，通常超过了其他微生物系统的生产率。系统地研究了克隆变异性，并制定了规避非靶向事件的策略，从而简化了筛选程序。具有新颖监管特性的启动子是从现有的启动子中发现或改造而成的。通过转让流行的操纵和组装技术以及创造新的技术，提高了遗传易处理性。第二代测序项目最终创造了第二个功能最佳的带注释酵母基因组。结合具有里程碑意义的生理学见识和增加的组学数据输出，为创建精细的基因组规模的代谢模型奠定了良好的基础。基于模型的代谢工程在人体中的首次应用P。pastoris展示了这种方法的潜力。建立酵母过氧化物酶体以进行分区代谢产物合成的最新努力似乎与经过研究的P的高容量过氧化物酶体机制非常吻合。帕斯托里斯（Pastoris）。在这里，为了支持在P中建立系统代谢工程，收集并审查了这些最新进展。帕斯托里斯（Pastoris）。