生物技术通报2025，Vol.41Issue(8)：74-81,8.DOI:10.13560/j.cnki.biotech.bull.1985.2025-0095
稀有密码子串联介导的HemB表达弱化提升5-氨基乙酰丙酸的含量
Enhancing 5-Aminolevulinic Acid Biosynthesis through Tandem Rare Codon-mediated Attenuation of HemB Expression
摘要
Abstract
[Objective]To reduce 5-aminolevulinic acid degradation and enhance its accumulation,the expression of 5-aminolevulinic acid dehydratase(HemB),which is a key enzyme in the catabolic pathway of 5-aminolevulinic acid(5-ALA),was attenuated via a tandem rare codon engineering strategy.[Method]Corynebacterium glutamicum was used as the chassis cell for the synthesis of 5-ALA.To reduce the catabolism of 5-ALA,tandem rare codons according to codon usage bias of C.glutamicum were introduced at the 5'end of the gene encoding HemB to weaken its expression.[Result]The metabolically engineered C.glutamicum strain showed a reduced growth rate,simultaneously the content of 5-ALA degradation intermediates decreased and 5-ALA accumulation was significantly enhanced in the fermentation broth.[Conclusion]The rare codon engineering strategy effectively attenuates HemB expression to enhance 5-ALA accumulation,and this strategy can be applied to fine-tuning expression of other proteins and remodeling other metabolic pathways.关键词
谷氨酸棒杆菌/5-氨基乙酰丙酸脱水酶/5-氨基乙酰丙酸/弱化表达/稀有密码子Key words
Corynebacterium glutamicum/5-aminolevulinic acid dehydratase/5-aminolevulinic acid/attenuating expression/rare codon引用本文复制引用
李加仪,李尽益,白雪,柏映国,刘波,张志伟..稀有密码子串联介导的HemB表达弱化提升5-氨基乙酰丙酸的含量[J].生物技术通报,2025,41(8):74-81,8.基金项目
国家重点研发计划(2022YFD1300703),国家自然科学基金项目(32472951) （2022YFD1300703）
