Engineering yeast membranes with mimetic and custom architecture for improved performance in biotechnological applications

具有模拟和定制结构的工程酵母膜可提高生物技术应用的性能

• 批准号: RGPIN-2022-04360
• 负责人: Ignea, Codruta
• 金额: $ 2.84万
• 依托单位: McGill University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=744453
• 关键词: Engineering; yeast; membranes; mimetic; custom

Yeast is a workhorse of modern biotechnology, preferred by industry due to its robustness and versatility. A broad range of products from medicines to small molecules, enzymes and vaccines, components of human breast milk, heme for meat substitutes, bioplastics, biomaterials and even biofuels are nowadays produced in yeast. Despite extensive efforts to understand and engineer efficient yeast cell factories, less attention has been placed on studying yeast membrane properties and their contribution to biotechnological applications. Several processes, both physiological or engineered, are greatly related to membranes, and could be limiting the performance of yeast cell factories. Current approaches mainly address the role of biological membranes as the primary target of the toxic effects of compounds produced in heterologous hosts. In reverse, there is little understanding of, or ability to predict, how differences in membrane composition of the host microorganism versus native membranes affect functional capacity of biosynthetic enzymes of different origin and interfere with intracellular transport of metabolites and their export outside of the cell. The long-term goal of the proposed research is to engineer the next generation of production platforms for biotechnological applications taking in consideration the role of biological membranes. In the short-term, we will directly address aspects related to membrane role in functionality of heterologous enzymes and pathways by modifying the yeast membrane composition to mimic that of producer organisms or by engineering non-natural yeast membranes. Thus, we will develop Phyto-yeast by biomimicking plant membrane or tailored yeast by design, and repurpose lipid droplets into storage compartments of target compounds. Using these platforms, we will evaluate the performance of model terpenoid biosynthetic pathways and formation of metabolic complexes. This program will benefit both the research scientific community and Canadian industry. We endeavor to develop advanced yeast chasses that will enable accessing high-value molecules with interesting biological activities and offer sustainable solutions to chemical production. Consequently, these compounds can be more broadly exploited for medicinal, agricultural, and other industrial applications. The knowledge developed here will provide the field with effective approaches to study and engineer biological membranes and the related processes. It will also foster innovations in industry and will address Canadian priorities for commercial R&D and manufacturing activities. Improved production platforms capable of accelerating time to market and increasing economic gain will highly benefit the Canadian economy. Thus, the relevance of this research program for the years ahead span multiple levels, including advancing scientific discoveries, tackling current and future industrial challenges, and building strong underpinning for novel strategies and innovations.

酵母是现代生物技术的主力，由于其稳健性和多功能性而受到工业界的青睐。如今，从药物到小分子、酶和疫苗、母乳成分、肉类替代品的血红素、生物塑料、生物材料甚至生物燃料等广泛的产品都是在酵母中生产的。尽管广泛的努力，了解和工程有效的酵母细胞工厂，较少的注意力已经放在研究酵母膜特性及其对生物技术应用的贡献。一些过程，无论是生理的还是工程的，都与膜有很大的关系，并且可能限制酵母细胞工厂的性能。目前的方法主要解决生物膜作为异源宿主中产生的化合物的毒性作用的主要靶标的作用。相反，很少有理解或预测能力，宿主微生物的膜组成与天然膜的差异如何影响不同来源的生物合成酶的功能能力，并干扰代谢物的细胞内转运及其输出到细胞外。 拟议研究的长期目标是设计下一代生物技术应用的生产平台，同时考虑生物膜的作用。在短期内，我们将直接解决与异源酶和途径的功能性膜的作用，通过修改酵母膜的组成，以模仿生产生物体或工程非天然酵母膜。因此，我们将通过仿生植物膜或设计定制酵母来开发植物酵母，并将脂滴重新用于目标化合物的储存室。使用这些平台，我们将评估模型萜类化合物生物合成途径和代谢复合物形成的性能。 该计划将有利于研究科学界和加拿大工业。我们奋进于开发先进的酵母菌槽，以获得具有有趣生物活性的高价值分子，并为化学生产提供可持续的解决方案。因此，这些化合物可以更广泛地用于医药，农业和其他工业应用。这里开发的知识将提供有效的方法来研究和工程生物膜和相关过程的领域。它还将促进工业创新，并将处理加拿大商业研发和制造活动的优先事项。改进的生产平台能够加快上市时间并增加经济收益，这将使加拿大经济受益匪浅。因此，该研究计划在未来几年的相关性跨越多个层面，包括推进科学发现，应对当前和未来的工业挑战，以及为新战略和创新奠定坚实的基础。