A synthetic yeast methanotroph for methane based sustainable biomanufacturing - SynYeast

甲烷是天然气的主要成分，是一种强大的温室气体，推动气候变化。最近全球甲烷排放量的增加和天然气储量的丰富，促使人们有兴趣利用这种碳化合物作为液体燃料和增值化学品生物生产的工业原料。然而，还没有将甲烷直接转化为甲醇的方法以工业规模商业化。生物基制造可以提供新的解决方案。甲烷氧化菌中的颗粒状甲烷单加氧酶（pMMO）是一种选择性催化剂，在温和条件下催化甲烷活化转化为甲醇。因此，许多焦点集中在该酶在平台菌株如E.大肠杆菌来开发“合成甲烷氧化菌”。然而，在E.由于这种酶的膜结合性质和甲醇的毒性，巴斯德毕赤酵母是一种高效的甲基营养菌，具有天然的甲醇同化途径和用于膜蛋白生产的既定宿主。该项目将在毕赤酵母膜中表达pMMO，以实现生物甲烷转化。该菌株将被进一步改造，以证明从甲烷生产高价值产品- 3-羟基丙酸（塑料的前体）。这种工程酵母将允许快速的设计-构建-测试周期，非常适合工业规模。在研究员明确潜力的基础上，在精心选择的宿主/共同宿主的监督和培训下，这个创新项目将在标准平台菌株中建立合成甲烷营养，用于生产有价值的产品，支持可持续的循环经济。

Methane, the principal component of natural gas, is a powerful greenhouse gas driving climate change. Recent rises in global methane emission and the abundance of natural gas reserves have prompted interest in exploiting this one carbon compound as an industrial feedstock for bioproduction of liquid fuels and value-added chemicals. However, no direct methane to methanol conversion process have been commercialized at industrial scale. Bio-based manufacturing could provide novel solutions. The particulate methane monooxygenase (pMMO) found in methanotrophic bacteria is a selective catalyst for methane activation and conversion to methanol under mild conditions. Hence, much focus has been on heterologous expression of this enzyme in platform strains like E. coli to develop 'synthetic methanotrophs'. However, no scalable methane conversion has been demonstrated in E. coli due to the membrane-bound nature of this enzyme and the toxicity of methanol. Pichia pastoris is an efficient methylotroph with a native methanol assimilation pathway and an established host for membrane protein production. This project will express pMMO in the Pichia membrane to enable biological methane conversion. This strain will be further engineered to demonstrate the production of the high value product- 3-hydroxy propionic acid (a precursor of plastics) from methane. This engineered yeast will allow for rapid design-build-test cycles and is well-suited for industrial scale up. Building on a the Fellow's clear potential, with supervision and training at carefully chosen host/cohost, this innovative project will establish synthetic methanotrophy in a standard platform strain for production of valuable products, underpinning a sustainable circular economy.