赖氨酸工业发展的机遇与挑战
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摘要
赖氨酸作为动物和人类营养的第一限制性氨基酸,在饲料添加剂、食品、医药行业有着广泛的应用。中国是赖氨酸生产和出口的第一大国,然而中国自有赖氨酸工业菌种水平较低,知识产权布局薄弱,而国外大公司通过长期投入育种工作建立了有竞争性的菌种及其全面的知识产权布局。合成生物学的迅速发展为工业菌种设计改造提供了全新的技术手段,有可能实现我国自有菌种的快速革新,为国内赖氨酸行业参与全球竞争提供新的机遇。主要介绍了赖氨酸工业当前的市场、技术和知识产权现状,以及赖氨酸工业发展机遇。
As the first limiting amino acid of animals and humans, lysine are widely used in feed additives, food and pharmaceutical industries. China is the largest lysine producer and exporter. However, the production performance of lysine industrial strains possessed by Chinese companies is low and the intellectual properties are not well covered for these strains. After long-time investment and development, several foreign companies established highly competitive strains which were well protected via patents. The rapid development of synthetic biology provides new opportunities to rapidly develop our own strains and build competence priorities for our companies in the international market. This article mainly presents the current market, technology and intellectual property of lysine industry, as well as the opportunities for the development of lysine industry.
As the first limiting amino acid of animals and humans, lysine are widely used in feed additives, food and pharmaceutical industries. China is the largest lysine producer and exporter. However, the production performance of lysine industrial strains possessed by Chinese companies is low and the intellectual properties are not well covered for these strains. After long-time investment and development, several foreign companies established highly competitive strains which were well protected via patents. The rapid development of synthetic biology provides new opportunities to rapidly develop our own strains and build competence priorities for our companies in the international market. This article mainly presents the current market, technology and intellectual property of lysine industry, as well as the opportunities for the development of lysine industry.
引文
[1]中国淀粉工业协会.赖氨酸行业现状及展望[EB/OL].(2017-02-01)[2018-11-30].http://www.siacn.org/index.php?optionid=1113&auto_id=26142.
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[4]王家勤.赖氨酸生产与应用发展概况[J].精细与专用化学品,2003,11(24):3-5.
[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]王宏龄,富春江.国内外氨基酸市场分析(二)[J].精细与专用化学品,2004,12(2):17-20.
[7]Kyowa Hakko Kogyo Co.,Ltd.Mutated 6-phosphogluconate dehydrogenase:EP1462516[P].2004-09-29.
[8]Kyowa Yowa Hakko Bio Co.,Ltd.Novel polynucleotides:EP2107128[P].2009-10-07.
[9]Kyowa Hak ko Kog yo Co.,Ltd.Novel poly nucleotides:EP1108790[P].2001-06-20.
[10]MASATO I,NORIO N,MASAKAZU O,et al.A third glucose uptake bypass in Corynebacterium glutamicum ATCC 31833[J].Applied Microbiology and Biotechnology,2015,99:2741-2750.
[11]Kyowa Hakko Kogyo Co.,Ltd.Novel desensitized aspartokinase:EP1172437[P].2002-01-16.
[12]Univ Hamburg Tech,Tutech Innovation Gmbh.Modified aspartate kinase from corynebacterium and its application for amino acid production:EP2374873[P].2011-10-12.
[13]MASATO I,JUNKO O,MIKIRO H,et al.A genome-based approach to create a minimally mutated Corynebacterium glutamicum strain for effi cient L-lysine production[J].Journal of Industrial Microbiology&Biotechnology,2006,33:610-615.
[14]Ajinomoto Co.,Ltd.Process for producing L-lysine by fermentation:WO1995016042[P].1995-06-15.
[15]WENDISCH V F.Amino acid biosynthesis-pathways,regulation and metabolic engineering[M].Berlin Heidelberg:Springer,2007:39-70.
[16]Ajinomoto Co.,Ltd.Method for producing L-lysine or L-threonine using Escherichia bacteria having attnuated malic enzyme activity:WO2005010175[P].2005-02-03.
[17]Cofco Biochemical Auhui Co.,Ltd.Tianjin Inst Ind Biotechnology CAS.Mutant aspurtokinuse III and the host cell and application:WO2014059789[P].2014-04-24.
[18]Ningxia Eppen Biotech Co.,Ltd.L-lysine generation method by fermenting bacteria having modifi ed aconitase gene and/or regulatory element:WO2014121669[P].2014-08-14.
[19]ZHANG Y,CAI J,SHANG X,et al.A new genome-scale metabolic model of Corynebacterium glutamicum and its application[J].Biotechnology for Biofuels,2017,10(169):1-16.
[20]JIANG Y,QIAN F,YANG J,et al.CRISPR-Cpf1 assisted genome editing of Corynebacterium glutamicum[J].Nature Communications,2017,8:15179.
[21]LIU J,WANG Y,LU Y,et al.Development of a CRISPR/Cas9 genome editing toolbox for Corynebacterium glutamicum[J].Microbial Cell Factories,2017,16(1):205.
[22]WANG Y,LIU Y,LIU J,et al.MACBETH:multiplex automated,Corynebacterium glutamicum,base editing method[J].Metabolic Engineering,2018,47:200-210.
[2]田金宝,贾晓波,杨志恒,等.L-赖氨酸的应用、生产及市场展望[J].氨基酸和生物资源,2004,26(1):44-46.
[3]周伟.浅谈赖氨酸行业现状和发展趋势[J].发酵科技通讯,2007,36(3):31-35.
[4]王家勤.赖氨酸生产与应用发展概况[J].精细与专用化学品,2003,11(24):3-5.
[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]王宏龄,富春江.国内外氨基酸市场分析(二)[J].精细与专用化学品,2004,12(2):17-20.
[7]Kyowa Hakko Kogyo Co.,Ltd.Mutated 6-phosphogluconate dehydrogenase:EP1462516[P].2004-09-29.
[8]Kyowa Yowa Hakko Bio Co.,Ltd.Novel polynucleotides:EP2107128[P].2009-10-07.
[9]Kyowa Hak ko Kog yo Co.,Ltd.Novel poly nucleotides:EP1108790[P].2001-06-20.
[10]MASATO I,NORIO N,MASAKAZU O,et al.A third glucose uptake bypass in Corynebacterium glutamicum ATCC 31833[J].Applied Microbiology and Biotechnology,2015,99:2741-2750.
[11]Kyowa Hakko Kogyo Co.,Ltd.Novel desensitized aspartokinase:EP1172437[P].2002-01-16.
[12]Univ Hamburg Tech,Tutech Innovation Gmbh.Modified aspartate kinase from corynebacterium and its application for amino acid production:EP2374873[P].2011-10-12.
[13]MASATO I,JUNKO O,MIKIRO H,et al.A genome-based approach to create a minimally mutated Corynebacterium glutamicum strain for effi cient L-lysine production[J].Journal of Industrial Microbiology&Biotechnology,2006,33:610-615.
[14]Ajinomoto Co.,Ltd.Process for producing L-lysine by fermentation:WO1995016042[P].1995-06-15.
[15]WENDISCH V F.Amino acid biosynthesis-pathways,regulation and metabolic engineering[M].Berlin Heidelberg:Springer,2007:39-70.
[16]Ajinomoto Co.,Ltd.Method for producing L-lysine or L-threonine using Escherichia bacteria having attnuated malic enzyme activity:WO2005010175[P].2005-02-03.
[17]Cofco Biochemical Auhui Co.,Ltd.Tianjin Inst Ind Biotechnology CAS.Mutant aspurtokinuse III and the host cell and application:WO2014059789[P].2014-04-24.
[18]Ningxia Eppen Biotech Co.,Ltd.L-lysine generation method by fermenting bacteria having modifi ed aconitase gene and/or regulatory element:WO2014121669[P].2014-08-14.
[19]ZHANG Y,CAI J,SHANG X,et al.A new genome-scale metabolic model of Corynebacterium glutamicum and its application[J].Biotechnology for Biofuels,2017,10(169):1-16.
[20]JIANG Y,QIAN F,YANG J,et al.CRISPR-Cpf1 assisted genome editing of Corynebacterium glutamicum[J].Nature Communications,2017,8:15179.
[21]LIU J,WANG Y,LU Y,et al.Development of a CRISPR/Cas9 genome editing toolbox for Corynebacterium glutamicum[J].Microbial Cell Factories,2017,16(1):205.
[22]WANG Y,LIU Y,LIU J,et al.MACBETH:multiplex automated,Corynebacterium glutamicum,base editing method[J].Metabolic Engineering,2018,47:200-210.