关键词: 甲醇, 毕赤酵母, 重组蛋白, 代谢工程, 合成生物学

Abstract:

As green and sustainable low-carbon feedstocks without competition with people for food, methanol and other C₁ compounds have great potential for advancement of biomanufacturing. Pichia pastoris (P. pastoris),as an industrial strain capable of naturally utilizing methanol, has a long history of research and has been widely employed in the biomanufacturing of various recombinant proteins. It has become an excellent chassis cell factory for methanol utilization. In recent years, there has been progress in understanding the microbial physiology, methanol metabolism networks, protein secretion expression pathways, and the identification of key components in P. pastoris. However, several critical challenges remain that limit its efficient application, such as limited understanding of the complex mechanisms of cell toxicity caused by methanol and its metabolites, insufficient capacity to explore “biological dark matters” related to cell robustness and methanol utilization, and restricted engineering approaches for efficiently converting methanol into target proteins. This review summarizes the research progress on the bioconversion of methanol into recombinant proteins by P. pastoris, with the emphasis on discussing how to optimize the methanol conversion and protein expression in P. pastoris cell factory. Finally, we address the challenges encountered in the recombinant protein production from methanol in P. pastoris and provide an outlook on its future biotechnology innovation and potential application.

Key words: methanol, Pichia pastoris, recombinant proteins, metabolic engineering, synthetic biology