Biotransformation of one-carbon resources by yeast

doi:10.16085/j.issn.1000-6613.2022-1490

Abstract

Abstract:

Under the current increasingly severe climate and energy crisis, there is an urgent need to reduce dependence on fossil fuels and utilize cleaner and sustainable feedstocks such as one-carbon resources including methanol, formic acid and carbon dioxide. Yeast, as a eukaryotic organism, has great potential in the biotransformation of one-carbon compounds due to the existence of organelles, which can isolate the toxic substances produced during the metabolism of one-carbon compounds. Recently, with the in-depth understanding of methanol metabolism pathways and the gradual improvement of genetic manipulation tools, many advances have been made in producing chemicals from methanol using natural methylotrophic yeasts. Also, the development of commonly used industrial yeasts such as Saccharomyces cerevisiae and Yarrowia lipolytica as synthetic methylotrophic yeasts has also achieved remarkable achievements. Herein the research progress of yeast chassis in the transformation and utilization of one-carbon raw materials is focused. Further, the current bottlenecks and potential solutions for the biotransformation of one-carbon resources are analyzed. With the development of more precise and efficient tools and the interpretation of cellular metabolic networks, the biotransformation of one-carbon resources by yeasts will play an increasingly important role in the future of green biomanufacturing.

Key words: methanol, formic acid, carbon dioxide fixation, synthetic biology, metabolic engineering

摘要：

在当前日趋严重的气候与能源危机下，传统的化工行业亟需减少对化石燃料的依赖，转而开发利用更为清洁可持续的原料，如包括甲醇、甲酸和二氧化碳等在内的一碳资源。作为真核生物的酵母由于细胞器的存在能够隔绝一碳化合物代谢过程中产生的有毒物质渗入细胞质对细胞产生毒害，在一碳化合物的生物转化中极具潜力。近年来，随着对甲醇代谢途径愈发深入地了解以及遗传操作工具的逐步完善，利用天然甲醇酵母以甲醇作为碳源生产化学品取得了重要进展。同时，开发常用的工业酵母如酿酒酵母、解脂耶氏酵母为人工甲基营养型酵母，实现将一碳资源进行高值化转化也取得了不俗的成就。本文着重讨论了酵母底盘在转化利用一碳原料方面的研究进展，在此基础上讨论并分析了目前一碳资源生物转化存在的瓶颈以及潜在的解决方案，指出随着更多精准高效的工具的开发以及对细胞代谢网络的阐释，依托酵母细胞进行一碳资源的生物转化将在未来的绿色生物制造中扮演越来越重要的角色。

关键词: 甲醇, 甲酸, 二氧化碳固定, 合成生物学, 代谢工程

CLC Number:

GUO Feng, ZHANG Shangjie, JIANG Yujia, JIANG Wankui, XIN Fengxue, ZHANG Wenming, JIANG Min. Biotransformation of one-carbon resources by yeast[J]. Chemical Industry and Engineering Progress, 2023, 42(1): 30-39.

郭峰, 张尚杰, 蒋羽佳, 姜万奎, 信丰学, 章文明, 姜岷. 一碳资源在酵母中的利用与转化[J]. 化工进展, 2023, 42(1): 30-39.

Figures/Tables 5

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产品	宿主	共底物	产量	参考文献
达马烯二醇-Ⅱ	毕赤酵母	无	1mg/g	[28]
洛伐他汀	毕赤酵母	甘油	419mg/L	[32]
莫纳可林 J	毕赤酵母	甘油	594mg/L	[31]
苹果酸	毕赤酵母	无	0.75g/L	[10]
苹果酸	毕赤酵母	酵母粉	2.79g/L	[10]
脂肪酸	毕赤酵母	无	23.4g/L	[22]
脂肪醇	毕赤酵母	无	2.0g/L	[22]
谷胱甘肽	多形汉逊酵母	无	0.25g/L	[33]
脂肪酸	多形汉逊酵母	无	15.9g/L	[23]

产品	宿主	共底物	产量	参考文献
达马烯二醇-Ⅱ	毕赤酵母	无	1mg/g	[28]
洛伐他汀	毕赤酵母	甘油	419mg/L	[32]
莫纳可林 J	毕赤酵母	甘油	594mg/L	[31]
苹果酸	毕赤酵母	无	0.75g/L	[10]
苹果酸	毕赤酵母	酵母粉	2.79g/L	[10]
脂肪酸	毕赤酵母	无	23.4g/L	[22]
脂肪醇	毕赤酵母	无	2.0g/L	[22]
谷胱甘肽	多形汉逊酵母	无	0.25g/L	[33]
脂肪酸	多形汉逊酵母	无	15.9g/L	[23]

底物	共底物	宿主	研究策略	成果	参考文献
甲醇	酵母粉	酿酒酵母	异源引入来源于毕赤酵母的甲醇同化途径	消耗2.35g/L甲醇，细胞生长增长11.70%，积累0.26g/L丙酮酸	[11]
甲醇	酵母粉	酿酒酵母	实验室适应性驯化	揭示了酿酒酵母存在天然的甲醇同化机制	[12]
甲醇	无	解脂耶氏酵母	异源表达杂合的RuMP和XuMP途径，敲除甲醛脱氢酶，强化Ru5P前体再生，适应性驯化	同化1.1g/L甲醇，在甲醇培养基下维持细胞不凋亡	[13]
甲酸，二氧化碳	葡萄糖	酿酒酵母	在甘氨酸缺陷型菌株中强化表达内源性还原性甘氨酸途径	实现甲酸依赖型的生长	[35]
二氧化碳	葡萄糖	酿酒酵母	异源引入一部分CBB循环基因	产物乙醇的产量提高10%，副产物甘油积累下降90%	[36]
二氧化碳	木糖	酿酒酵母	异源引入一部分CBB循环基因	产物乙醇的产量提高10%，副产物木糖醇积累下降90%	[37]
二氧化碳	甲醇	毕赤酵母	引入完整的CBB循环，敲除甲醇同化途径，适应性驯化	完全利用二氧化碳合成生物质，实现半自养	[38]

底物	共底物	宿主	研究策略	成果	参考文献
甲醇	酵母粉	酿酒酵母	异源引入来源于毕赤酵母的甲醇同化途径	消耗2.35g/L甲醇，细胞生长增长11.70%，积累0.26g/L丙酮酸	[11]
甲醇	酵母粉	酿酒酵母	实验室适应性驯化	揭示了酿酒酵母存在天然的甲醇同化机制	[12]
甲醇	无	解脂耶氏酵母	异源表达杂合的RuMP和XuMP途径，敲除甲醛脱氢酶，强化Ru5P前体再生，适应性驯化	同化1.1g/L甲醇，在甲醇培养基下维持细胞不凋亡	[13]
甲酸，二氧化碳	葡萄糖	酿酒酵母	在甘氨酸缺陷型菌株中强化表达内源性还原性甘氨酸途径	实现甲酸依赖型的生长	[35]
二氧化碳	葡萄糖	酿酒酵母	异源引入一部分CBB循环基因	产物乙醇的产量提高10%，副产物甘油积累下降90%	[36]
二氧化碳	木糖	酿酒酵母	异源引入一部分CBB循环基因	产物乙醇的产量提高10%，副产物木糖醇积累下降90%	[37]
二氧化碳	甲醇	毕赤酵母	引入完整的CBB循环，敲除甲醇同化途径，适应性驯化	完全利用二氧化碳合成生物质，实现半自养	[38]

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