Department of Energy Joint BioEnergy Institute, Emeryville, CA, 94608, USA.
Biosystems Design and Simulation Group, Environmental Molecular Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory, Richland, WA, 99352, USA.
Appl Microbiol Biotechnol. 2018 Oct;102(20):8621-8628. doi: 10.1007/s00253-018-9265-1. Epub 2018 Aug 4.
The secretion of enzymes used by fungi to digest their environment has been exploited by humans for centuries for food and beverage production. More than a century after the first biotechnology patent, we know that the enzyme cocktails secreted by these amazing organisms have tremendous use across a number of industrial processes. Secreting the maximum titer of enzymes is critical to the economic feasibility of these processes. Traditional mutagenesis and screening approaches have generated the vast majority of strains used by industry for the production of enzymes. Until the emergence of economical next generation DNA sequencing platforms, the majority of the genes mutated in these screens remained uncharacterized at the sequence level. In addition, mutagenesis comes with a cost to an organism's fitness, making tractable rational strain design approaches an attractive alternative. As an alternative to traditional mutagenesis and screening, controlled manipulation of multiple genes involved in processes that impact the ability of a fungus to sense its environment, regulate transcription of enzyme-encoding genes, and efficiently secrete these proteins will allow for rational design of improved fungal protein production strains.
真菌用来消化其环境的酶的分泌已被人类用于食品和饮料生产数百年。在第一个生物技术专利获得一个多世纪之后，我们知道这些神奇生物分泌的酶混合物在许多工业过程中具有巨大的用途。分泌最大浓度的酶对于这些过程的经济可行性至关重要。传统的诱变和筛选方法已经生成了工业中用于生产酶的绝大多数菌株。直到经济实惠的下一代 DNA 测序平台的出现，这些筛选中突变的大多数基因在序列水平上仍然没有特征。此外，诱变会对生物体的适应性造成代价，因此可处理的理性菌株设计方法成为一个有吸引力的替代方案。作为传统诱变和筛选的替代方案，对影响真菌感知其环境的能力、调节酶编码基因转录以及有效分泌这些蛋白质的过程中涉及的多个基因进行控制操作，将允许对提高真菌蛋白生产菌株进行合理设计。
