利用工程化毕赤酵母从单碳底物甲醇高效生产衣康酸。

Efficient production of itaconic acid from the single-carbon substrate methanol with engineered Komagataella phaffii.

作者信息

Severinsen Manja Mølgaard, Bachleitner Simone, Modenese Viola, Ata Özge, Mattanovich Diethard

机构信息

Department of Biotechnology, Institute of Microbiology and Microbial Biotechnology, BOKU University, 1190, Vienna, Austria.

Department of Food, Environmental and Nutritional Sciences, University of Milan, Milan, Italy.

出版信息

Biotechnol Biofuels Bioprod. 2024 Jul 15;17(1):98. doi: 10.1186/s13068-024-02541-1.

DOI:10.1186/s13068-024-02541-1

PMID:39010147

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11251334/

Abstract

BACKGROUND

Amidst the escalating carbon dioxide levels resulting from fossil fuel consumption, there is a pressing need for sustainable, bio-based alternatives to underpin future global economies. Single-carbon feedstocks, derived from CO, represent promising substrates for biotechnological applications. Especially, methanol is gaining prominence for bio-production of commodity chemicals.

RESULTS

In this study, we show the potential of Komagataella phaffii as a production platform for itaconic acid using methanol as the carbon source. Successful integration of heterologous genes from Aspergillus terreus (cadA, mttA and mfsA) alongside fine-tuning of the mfsA gene expression, led to promising initial itaconic acid titers of 28 g·L after 5 days of fed-batch cultivation. Through the combined efforts of process optimization and strain engineering strategies, we further boosted the itaconic acid production reaching titers of 55 g·L after less than 5 days of methanol feed, while increasing the product yield on methanol from 0.06 g·g to 0.24 g·g.

CONCLUSION

Our results highlight the potential of K. phaffii as a methanol-based platform organism for sustainable biochemical production.

摘要

背景

在化石燃料消耗导致二氧化碳水平不断上升的背景下，迫切需要可持续的生物基替代品来支撑未来的全球经济。源自一氧化碳的单碳原料是生物技术应用中很有前景的底物。特别是，甲醇在商品化学品的生物生产中越来越受到关注。

结果

在本研究中，我们展示了毕赤酵母作为以甲醇为碳源生产衣康酸的平台的潜力。来自土曲霉的异源基因（cadA、mttA和mfsA）的成功整合以及mfsA基因表达的微调，在分批补料培养5天后，衣康酸的初始滴度达到了28 g·L，前景可观。通过工艺优化和菌株工程策略的共同努力，我们进一步提高了衣康酸的产量，在甲醇进料不到5天的时间里，滴度达到了55 g·L，同时将甲醇上的产物产率从0.06 g·g提高到了0.24 g·g。