Development of second-generation S. cerevisiae hosts for enhanced protein yield and quality

重组蛋白表达是支持许多生物疗法生产的关键制造技术。存在大量的蛋白质表达系统，但大多数被批准用于临床使用的生物药物和蛋白质制品都是使用哺乳动物细胞培养技术制造的。这些制造过程费力、缓慢且昂贵。与哺乳动物细胞培养相比，酵母系统提供了一种更简单的大规模表达重组蛋白的方法，并且成本大大降低。许多酵母蛋白表达系统已经商业化。然而，最常用于工业生物制剂生产的面包酵母（Saccharomyces cerevisiae）表达系统本身从未被开发它们的公司广泛商业化。这些烘焙酵母系统的专利保护现在已经或即将到期。这就产生了相当大的自由，可以创建新系统，并围绕利用酿酒酵母作为蛋白质生产动力的增强型第二代蛋白质表达系统开发新的知识产权，并使这项技术广泛应用于希望将重组产品推向市场的新公司。该项目将使Phenotypeca能够开发出新的酿酒葡萄球菌菌株，这些菌株可以快速、轻松地进行定制，以优化重组蛋白的生产。在这种情况下，该平台将为另一家英国中小企业Invizius生产一种蛋白质（H-Guard），这是一种用于透析设备的涂层，可防止因反复暴露于透析膜而引起的炎症反应。Invizius将与过程创新中心（CPI）合作，该中心作为资助伙伴加入该联盟，进行工业发酵建模，以确定最适合规模化生产的方法。该项目支持Phenotypeca成为需要酿酒葡萄球菌蛋白表达系统的客户的服务提供商。目前还没有工业S. cerevisiae系统的商业供应商——工业上使用的所有S. cerevisiae系统都是由其他公司内部开发的专有系统，这些公司不想分享他们的技术或提供开发服务。Phenotypeca正试图克服市场对酿酒酵母蛋白表达系统的需求，特别是一类治疗性肽，其中毕赤酵母为基础的酵母系统无法满足质量和监管要求。

Recombinant protein expression is the keystone manufacturing technique supporting production of many biological therapies. A large number of protein expression systems exist, but the majority of biological drugs and protein products that are approved for clinical use have been manufactured using mammalian cell culture techniques. These manufacturing processes are laborious, slow, and expensive.Yeast systems offer a significantly simpler way of expressing recombinant proteins at scale compared to mammalian cell culture, and at a greatly reduced cost.A number of yeast protein expression systems have been commercialised. However, the baker's yeast (Saccharomyces cerevisiae) expression systems, which are most commonly used in industry for biologics production, have never themselves been widely commercialised by the companies that developed them. The patent protection for these baker's yeast systems has now expired or is expiring. This engenders considerable freedom to create new systems and develop new IP surrounding enhanced, second-generation protein expression systems utilising S. cerevisiae as their protein-production powerhouse and making this technology widely available to new companies wishing to bring recombinant products to the market.The project will enable Phenotypeca to develop novel strains of S. cerevisiae to be created that can be quickly and easily tailored to optimize production of recombinant proteins.In this instance, the platform will be exemplified by producing a protein (H-Guard) for another UK SME - Invizius - which is a coating used on dialysis equipment to prevent inflammatory responses induced by repeated exposure to dialyser membranes.Invizius will work alongside the Centre for Process Innovation (CPI), who join the consortium as grant funded partners to conduct industrial fermentation modelling to identify the most suitable for scale-up production.The project supports Phenotypeca to become a service provider for clients wanting S. cerevisiae-based protein expression systems. There are currently no commercial providers of industrial S. cerevisiae systems -- all S. cerevisiae systems used industrially are proprietary systems developed in-house by other companies who don't want to share their technology of offer a development service. Phenotypeca is attempting to overcome the unmet market need for S. cerevisiae protein expression systems, especially for a class of therapeutic peptides for which Pichia pastoris-based yeast systems cannot meet the quality and regulatory requirements.