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

IF 6.1 1区工程技术 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology for Biofuels Pub Date : 2024-07-15 DOI:10.1186/s13068-024-02541-1

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

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引用次数: 0

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 CO₂, 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⁻¹ 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⁻¹ after less than 5 days of methanol feed, while increasing the product yield on methanol from 0.06 g·g⁻¹ to 0.24 g·g⁻¹.

Conclusion

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

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利用改造的 Komagataella phaffii 从单碳底物甲醇中高效生产衣康酸。

背景：化石燃料的消耗导致二氧化碳含量不断攀升，因此迫切需要可持续的生物替代品来支撑未来的全球经济。从二氧化碳中提取的单碳原料是生物技术应用中前景广阔的基质。特别是甲醇在生物生产商品化学品方面的应用日益突出：在这项研究中，我们展示了以甲醇为碳源的 Komagataella phaffii 作为衣康酸生产平台的潜力。在对 mfsA 基因的表达进行微调的同时，成功整合了来自土曲霉的异源基因（cadA、mttA 和 mfsA），经过 5 天的分批进行喂养培养，最初的衣康酸滴度达到了 28 g-L-1。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产量，在喂养甲醇不到 5 天后，衣康酸滴度达到 55 g-L-1，同时甲醇产品产量从 0.06 g-g-1 提高到 0.24 g-g-1：我们的研究结果凸显了 K. phaffii 作为基于甲醇的可持续生化生产平台生物的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biotechnology for Biofuels 工程技术-生物工程与应用微生物

自引率

0.00%

发文量

审稿时长

2.7 months

期刊介绍： Biotechnology for Biofuels is an open access peer-reviewed journal featuring high-quality studies describing technological and operational advances in the production of biofuels, chemicals and other bioproducts. The journal emphasizes understanding and advancing the application of biotechnology and synergistic operations to improve plants and biological conversion systems for the biological production of these products from biomass, intermediates derived from biomass, or CO2, as well as upstream or downstream operations that are integral to biological conversion of biomass. Biotechnology for Biofuels focuses on the following areas: • Development of terrestrial plant feedstocks • Development of algal feedstocks • Biomass pretreatment, fractionation and extraction for biological conversion • Enzyme engineering, production and analysis • Bacterial genetics, physiology and metabolic engineering • Fungal/yeast genetics, physiology and metabolic engineering • Fermentation, biocatalytic conversion and reaction dynamics • Biological production of chemicals and bioproducts from biomass • Anaerobic digestion, biohydrogen and bioelectricity • Bioprocess integration, techno-economic analysis, modelling and policy • Life cycle assessment and environmental impact analysis