氨基酸产业现状及生产菌株选育技术
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摘要
综述了2017年我国氨基酸产能、产量及出口情况,系统介绍了氨基酸生产菌株选育技术.常规育种技术尚不过时,其应与反向代谢工程研究相结合.代谢工程育种技术经过多年的发展,已经取得了长足的进步,从常规代谢工程发展为系统代谢工程,同时进化代谢工程也展现出巨大的应用价值.工业化菌株构建需在基因组水平操作,介绍了氨基酸生产菌种大肠杆菌和谷氨酸棒杆菌基因组编辑技术的现状.最后,简要介绍了精确代谢调控技术,包括基因表达的强化和弱化策略,并给出了应用实例.
This paper summarized the amino acid production capacity,production and export volumn of China in 2017.The breeding technologies of amino acid producing strains were elucidated.The traditional strain breeding technology has not been out-of-date.Instead,it should be integrated into the study of reverse metabolic engineering.Metabolic engineering has achieved great progress through many yearsdevelopment,and moved into systematic metabolic engineering.Meanwhile,the evolutionary metabolic engineering has shown great potential.The construction of industrial strains is often operated at the genome level.Therefore,this paper introduces the genome editing technologies of Escherichia coli and Corynebacterium glutamicum.Finally,precise metabolic regulation technologies are briefly introduced,and a case study is also provided.
This paper summarized the amino acid production capacity,production and export volumn of China in 2017.The breeding technologies of amino acid producing strains were elucidated.The traditional strain breeding technology has not been out-of-date.Instead,it should be integrated into the study of reverse metabolic engineering.Metabolic engineering has achieved great progress through many yearsdevelopment,and moved into systematic metabolic engineering.Meanwhile,the evolutionary metabolic engineering has shown great potential.The construction of industrial strains is often operated at the genome level.Therefore,this paper introduces the genome editing technologies of Escherichia coli and Corynebacterium glutamicum.Finally,precise metabolic regulation technologies are briefly introduced,and a case study is also provided.
引文
[1]王洪荣,季昀.氨基酸的生物活性及其营养调控功能的研究进展[J].动物营养学报,2013,25(3):447-457.
[2]EGGELING L,SAHM H.L-glutamate and L-lysine:traditional products with impetuous developments[J].Applied microbiology and biotechnology,1999,52(2):146-153.
[3]陈宁,范晓光.氨基酸生产菌株的研究热点及发展动向[J].发酵科技通讯,2016,45(1):1-6.
[4]张权威,林高扬,马倩.组学技术在氨基酸生产菌株选育中的研究现状与发展趋势[J].发酵科技通讯,2017,46(4):205-211.
[5]陈宁,范晓光.我国氨基酸产业现状及发展对策[J].发酵科技通讯,2017,46(4):193-197.
[6]中国生物发酵产业协会.中国生物发酵产业协会二届六次理事会暨二届六次常务理事会文件汇编[C].北京:中国生物发酵产业协会,2017,北京.
[7]FAN X G,WU H Y,LI G L,et al.Improvement of uridine production of Bacillus subtilis by atmospheric and room temperature plasma mutagenesis and high throughput screening[J].Plos one,2017,12(5):e0176545.
[8]OHNISHI J,MITSUHASHI S,HAYASHI M,et al.A novel methodology employing Corynebacterium glutamicum genome information to generate a new L-lysine-producing mutant[J].Applied microbiology and biotechnology,2002,58(2):217-223.
[9]IKEDA M,OHNISHI J,HAYASHI M,et al.A genomebased approach to create a minimally mutated Corynebacterium glutamicumstrain for efficient L-lysine production[J].Journal of industrial microbiology and biotechnology,2006,33(7):610-615.
[10]LI Y J,WEI H B,WANG T,et al.Current status on metabolic engineering for the production of l-aspartate family amino acids and derivatives[J].Bioresource technology,2017,245:1588-1602.
[11]MA Q,ZHANG Q W,XU Q Y,et al.Systems metabolic engineering strategies for the production of amino acids[J].Synthetic and systems biotechnology,2017,2(2):87-96.
[12]LEE K H,Park J H,Kim T Y,et al.Systems metabolic engineering of Escherichia coli for L-threonine production[J].Molecular systems biology,2007,3(1):2025.
[13]BECKER J,ZELDER O,HFNER S,et al.From zero to hero-design-based systems metabolic engineering of Corynebacterium glutamicum for L-lysine production[J].Metabolic engineering,2011,13(2):159-168.
[14]WANG J,ZHANG Y,CHEN Y,et al.Global regulator engineering significantly improved Escherichia coli tolerances toward inhibitors of lignocellulosic hydrolysates[J].Biotechnology and bioengineering,2012,109(12):3133-3142.
[15]FANG M,WANG T,ZHANG C,et al.Intermediate-sensor assisted push-pull strategy and its application in heterologous deoxyviolacein production in Escherichia coli[J].Metabolic engineering,2016,33:41-51.
[16]SCHWENTNER A,FEITH A,MNCH E,et al.Metabolic engineering to guide evolution-Creating a novel mode for Lvaline production with Corynebacterium glutamicum[J].Metabolic engineering,2018,47:31-41.
[17]DATSENKO K A,WANNER B L.One-step inactivation of chromosomal genes in Escherichia coli K-12using PCR products[J].Proceedings of the national academy of sciences of the United States of America,2000,97(12):6640-6645.
[18]LI Y F,LIN Z Q,HUANG C,et al.Metabolic engineering of Escherichia coli using CRISPR-Cas9meditated genome editing[J].Metabolic engineering,2015,31:13-21.
[19]CHO J S,CHOI K R,CPS P,et al.CRISPR/Cas9-coupled recombineering for metabolic engineering of Corynebacterium glutamicum[J].Metabolic engineering,2017,42:157-167.
[20]LIU J,WANG Y,Lu,Y J,et al.Development of a CRISPR/Cas9genome editing toolbox for Corynebacterium glutamicum[J].Microbial cell factories,2017,16(1):205.
[21]PENG F,WANG X Y,SUN Y,et al.Efficient gene editing in Corynebacterium glutamicum using the CRISPR/Cas9system[J].Microbial cell factories,2017,16(1):201.
[22]WANG Y,LIU Y,LIU J,et al.Macbeth:multiplex automated Corynebacterium glutamicum,base editing method[J].Metabolic engineering,2018,47:200-210.
[23]NING Y K,WU X J,ZHANG C L,et al.Pathway construction and metabolic engineering for fermentative production of ectoine in Escherichia coli[J].Metabolic engineering,2016,36:10-18.
[2]EGGELING L,SAHM H.L-glutamate and L-lysine:traditional products with impetuous developments[J].Applied microbiology and biotechnology,1999,52(2):146-153.
[3]陈宁,范晓光.氨基酸生产菌株的研究热点及发展动向[J].发酵科技通讯,2016,45(1):1-6.
[4]张权威,林高扬,马倩.组学技术在氨基酸生产菌株选育中的研究现状与发展趋势[J].发酵科技通讯,2017,46(4):205-211.
[5]陈宁,范晓光.我国氨基酸产业现状及发展对策[J].发酵科技通讯,2017,46(4):193-197.
[6]中国生物发酵产业协会.中国生物发酵产业协会二届六次理事会暨二届六次常务理事会文件汇编[C].北京:中国生物发酵产业协会,2017,北京.
[7]FAN X G,WU H Y,LI G L,et al.Improvement of uridine production of Bacillus subtilis by atmospheric and room temperature plasma mutagenesis and high throughput screening[J].Plos one,2017,12(5):e0176545.
[8]OHNISHI J,MITSUHASHI S,HAYASHI M,et al.A novel methodology employing Corynebacterium glutamicum genome information to generate a new L-lysine-producing mutant[J].Applied microbiology and biotechnology,2002,58(2):217-223.
[9]IKEDA M,OHNISHI J,HAYASHI M,et al.A genomebased approach to create a minimally mutated Corynebacterium glutamicumstrain for efficient L-lysine production[J].Journal of industrial microbiology and biotechnology,2006,33(7):610-615.
[10]LI Y J,WEI H B,WANG T,et al.Current status on metabolic engineering for the production of l-aspartate family amino acids and derivatives[J].Bioresource technology,2017,245:1588-1602.
[11]MA Q,ZHANG Q W,XU Q Y,et al.Systems metabolic engineering strategies for the production of amino acids[J].Synthetic and systems biotechnology,2017,2(2):87-96.
[12]LEE K H,Park J H,Kim T Y,et al.Systems metabolic engineering of Escherichia coli for L-threonine production[J].Molecular systems biology,2007,3(1):2025.
[13]BECKER J,ZELDER O,HFNER S,et al.From zero to hero-design-based systems metabolic engineering of Corynebacterium glutamicum for L-lysine production[J].Metabolic engineering,2011,13(2):159-168.
[14]WANG J,ZHANG Y,CHEN Y,et al.Global regulator engineering significantly improved Escherichia coli tolerances toward inhibitors of lignocellulosic hydrolysates[J].Biotechnology and bioengineering,2012,109(12):3133-3142.
[15]FANG M,WANG T,ZHANG C,et al.Intermediate-sensor assisted push-pull strategy and its application in heterologous deoxyviolacein production in Escherichia coli[J].Metabolic engineering,2016,33:41-51.
[16]SCHWENTNER A,FEITH A,MNCH E,et al.Metabolic engineering to guide evolution-Creating a novel mode for Lvaline production with Corynebacterium glutamicum[J].Metabolic engineering,2018,47:31-41.
[17]DATSENKO K A,WANNER B L.One-step inactivation of chromosomal genes in Escherichia coli K-12using PCR products[J].Proceedings of the national academy of sciences of the United States of America,2000,97(12):6640-6645.
[18]LI Y F,LIN Z Q,HUANG C,et al.Metabolic engineering of Escherichia coli using CRISPR-Cas9meditated genome editing[J].Metabolic engineering,2015,31:13-21.
[19]CHO J S,CHOI K R,CPS P,et al.CRISPR/Cas9-coupled recombineering for metabolic engineering of Corynebacterium glutamicum[J].Metabolic engineering,2017,42:157-167.
[20]LIU J,WANG Y,Lu,Y J,et al.Development of a CRISPR/Cas9genome editing toolbox for Corynebacterium glutamicum[J].Microbial cell factories,2017,16(1):205.
[21]PENG F,WANG X Y,SUN Y,et al.Efficient gene editing in Corynebacterium glutamicum using the CRISPR/Cas9system[J].Microbial cell factories,2017,16(1):201.
[22]WANG Y,LIU Y,LIU J,et al.Macbeth:multiplex automated Corynebacterium glutamicum,base editing method[J].Metabolic engineering,2018,47:200-210.
[23]NING Y K,WU X J,ZHANG C L,et al.Pathway construction and metabolic engineering for fermentative production of ectoine in Escherichia coli[J].Metabolic engineering,2016,36:10-18.