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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2021, Vol. 41 Issue (1): 103-113    DOI: 10.13523/j.cb.2009004
综述     
吡咯喹啉醌生物合成研究进展 *
王光路,王梦园,周忆菲,马科,张帆,杨雪鹏()
郑州轻工业大学食品与生物工程学院 食品生产与安全河南省协同创新中心 郑州 450001
Research Progress in Pyrrologuinoline Quinone Biosynthesis
WANG Guang-lu,WANG Meng-yuan,ZHOU Yi-fei,MA Ke,ZHANG Fan,YANG Xue-peng()
School of Food and Bioengineering, Collaborative Innovation Center of Production and Safety, Zhengzhou University of Light Industry, Zhengzhou 450001, China
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摘要：

吡咯喹啉醌(pyrroloquinoline quinone,PQQ)是一种多肽修饰类天然产物,是继烟酰胺和核黄素之后第三类辅酶,具有抗氧化、抗衰老、提高免疫力等重要生理功能,在医药、保健等领域具有重要价值。目前,PQQ的大规模制备仍然存在诸多问题,限制了PQQ的广泛应用。当前迫切需求低成本的合成方式,以充分实现其广阔的应用潜力。综述了近年来PQQ生物合成途径的解析、关键酶的催化反应机理以及高产菌株选育等方面的研究动态及发展趋势,并针对PQQ生物合成微生物细胞工厂构建研究策略提出了建议及展望。
关键词： 吡咯喹啉醌;  生物合成途径;  调控机制;  关键酶    
Abstract:

Pyrroloquinoline quinone (PQQ) is a ribosomally synthesized and post-translationally modified peptide that has been recognized as the third class of redox cofactors in addition to the well-known nicotinamides (NAD(P)+) and flavins (FAD, FMN). It is widely distributed in organisms and has physiological functions such as antioxidation. It has broad application prospects in the fields of medicine, food and cosmetics. However, the lack of an efficient microbial cell factory limits the industrial production efficiency of PQQ. In this paper, we reviewed the current research on the biosynthesis pathway of PQQ, the structures of key enzymes, as well as metabolic engineering strategies for the construction of high-yielding strains. These advances will provide a basis for finally achieving stable PQQ biosynthesis in microbial cell factories.

Key words: Pyrroloquinoline quinine    Biosynthesis pathway    Regulation mechanism    Key enzymes
收稿日期: 2020-09-03 出版日期: 2021-02-09
ZTFLH:  Q56  
基金资助: * 国家自然科学基金(U1904101);河南省科技攻关重点研发与推广专项(202102310021);河南省科技攻关重点研发与推广专项(182102310607)
通讯作者: 杨雪鹏     E-mail: yangxuepeng@zzuli.edu.cn
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王光路
王梦园
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张帆
杨雪鹏

引用本文:

王光路, 王梦园, 周忆菲, 马科, 张帆, 杨雪鹏. 吡咯喹啉醌生物合成研究进展 *[J]. 中国生物工程杂志, 2021, 41(1): 103-113.

WANG Guang-lu, WANG Meng-yuan, ZHOU Yi-fei, MA Ke, ZHANG Fan, YANG Xue-peng. Research Progress in Pyrrologuinoline Quinone Biosynthesis. China Biotechnology, 2021, 41(1): 103-113.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2009004    或    https://manu60.magtech.com.cn/biotech/CN/Y2021/V41/I1/103

图1  PQQ的化学结构
图2  PQQ生物合成途径[14]
图3  PQQ碳骨架源于PqqA上谷氨酸和酪氨酸残基
图4  人工合成PqqA多肽三维结构
图5  PqqD协同PqqE在自由基反应中的催化作用
图6  PqqF/PqqG在PQQ合成发挥多肽水解作用[18]
图7  PqqB的Fe2+依赖的羟化反应[20]
图8  PqqC催化的反应: AHQQ的环化和八电子氧化
图9  M. extorquens AM1甲醇脱氢酶表达及PQQ合成的调控机制[36,37,38]
菌株 得率(mg/g) 产率[mg/(L·h)] 产量 (mg/L) 参考文献
Bacillus sp. 083114 - - 64.3 [40]
Methylopila sp. YHT-1 9 1.6 113.6 [41]
Methylovorus sp. strain MP68 - 0.9 125.0 [42]
Methylobacillus sp. zju323 105 2.2 162.2 [43]
Methylobacterium extorquens AM1 - - 54.0 [44]
Pseudomonas 0813 - - 425.7 [45]
Hyphomicrobium denitrificans FJNU-6 - 7.6 1 087.0 [46]
K. pneumoniae DSM 2026 - - 0.6 [50]
Gluconobacter oxydans 621H 0. 016 0.011 0.8 [54]
表1  吡咯喹啉醌筛选菌株生产性能分析
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