Abundant natural gas reserves, along with increased biogas production, have prompted recent interest in harnessing methane as an industrial feedstock for the production of liquid fuels and chemicals. Methane can either be used directly for fermentation or first oxidized to methanol via biological or chemical means. Methanol is advantageous due to its liquid state under normal conditions. Methylotrophy, defined as the ability of microorganisms to utilize reduced one-carbon compounds like methane and methanol as sole carbon and energy sources for growth, is widespread in bacterial communities. However, native methylotrophs lack the extensive and well-characterized synthetic biology toolbox of platform microorganisms like Escherichia coli, which results in slow and inefficient design-build-test cycles. If a heterologous production pathway can be engineered, the slow growth and uptake rates of native methylotrophs generally limit their industrial potential. Therefore, much focus has been placed on engineering synthetic methylotrophs, or non-methylotrophic platform microorganisms, like E. coli, that have been engineered with synthetic methanol utilization pathways. These platform hosts allow for rapid design-build-test cycles and are well-suited for industrial application at the current time. In this review, recent progress made toward synthetic methylotrophy (including methanotrophy) is discussed. Specifically, the importance of amino acid metabolism and alternative one-carbon assimilation pathways are detailed. A recent study that has achieved methane bioconversion to liquid chemicals in a synthetic E. coli methanotroph is also briefly discussed. We also discuss strategies for the way forward in order to realize the industrial potential of synthetic methanotrophs and methylotrophs.

丰富的天然气储量以及沼气产量的增加，促使人们最近对利用甲烷作为生产液体燃料和化学品的工业原料产生了兴趣。甲烷可以直接用于发酵，也可以先通过生物或化学方式氧化成甲醇。甲醇是有利的，因为它在正常条件下呈液态。甲基营养，定义为微生物利用减少的单碳化合物（如甲烷和甲醇）作为生长的唯一碳和能源的能力，在细菌群落中很普遍。然而，天然甲基营养菌缺乏平台微生物（如大肠杆菌）的广泛且特征明确的合成生物学工具箱，这会导致设计-构建-测试周期缓慢且效率低下。如果可以设计出异源生产途径，天然甲基营养菌的缓慢生长和吸收率通常会限制它们的工业潜力。因此，人们将重点放在工程合成甲基营养菌或非甲基营养平台微生物上，如大肠杆菌，已经用合成甲醇利用途径进行了工程设计。这些平台主机允许快速的设计-构建-测试周期，非常适合当前的工业应用。在这篇综述中，讨论了合成甲基营养菌（包括甲烷营养菌）的最新进展。具体来说，详细介绍了氨基酸代谢和替代一碳同化途径的重要性。还简要讨论了最近的一项研究，该研究已在合成大肠杆菌中将甲烷生物转化为液体化学品。我们还讨论了前进的策略，以实现合成甲烷氧化菌和甲基营养菌的工业潜力。