A synthetic yeast methanotroph for methane based sustainable biomanufacturing - SynYeast

甲烷是天然气的主要成分，是一种推动气候变化的强大温室气体。最近全球甲烷排放量的上升和天然气储量的丰富，促使人们有兴趣将这种碳化合物作为生物生产液体燃料和增值化学品的工业原料。然而，目前还没有甲烷直接转化为甲醇的工业化生产工艺。基于生物的制造可以提供新的解决方案。在甲烷营养细菌中发现的颗粒甲烷单加氧酶(PMMO)是甲烷活化和温和条件下转化为甲醇的选择性催化剂。因此，该酶在大肠杆菌等平台菌株中的异源表达一直是人们关注的焦点，以开发“合成甲烷氧化菌”。然而，由于这种酶的膜结合性质和甲醇的毒性，在大肠杆菌中还没有证明可扩展的甲烷转化。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，是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，以证明从甲烷中生产高价值产品-3-羟基丙酸(塑料的前体)。这种工程酵母将允许快速的设计-建造-测试周期，非常适合工业放大。这一创新项目以该研究员明确的潜力为基础，在精心选择的东道主/合作主持人的监督和培训下，将在标准平台菌株中建立合成甲烷营养素，用于生产有价值的产品，为可持续的循环经济奠定基础。

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.