CN104250650A - 一种δ6-脂肪酸脱氢酶基因及其应用 - Google Patents
一种δ6-脂肪酸脱氢酶基因及其应用 Download PDFInfo
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Abstract
本发明公开了一种从深黄被孢霉M6-22中分离的编码Δ6-脂肪酸脱氢酶的核苷酸序列,其核苷酸序列如SEQIDNO:1所示,该基因编码的氨基酸序列如SEQIDNO:2所示,通过构建重组载体并在酿酒酵母中表达,表达产物具有Δ6-脂肪酸脱氢酶功能,能催化亚油酸转化成γ-亚麻酸。
Description
技术领域
本发明属于生物技术领域和遗传工程领域,涉及从一种丝状真菌---毛霉属的深黄被孢霉(Mortierella isabellina)M6-22中克隆的Δ6-脂肪酸脱氢酶基因,并将该基因直接与不同载体连接,转入细菌、酵母、植物或动物中,利用其编码Δ6-脂肪酸脱氢酶产生包括γ-亚麻酸等多不饱和脂肪酸。
背景技术
γ-亚麻酸(γ-linolenic acid)是一种多功能油脂成分,是人体必需的多不饱和脂肪酸,具有多种重要的生理活性作用,在机体的生理调控和物质代谢上发挥着重要的作用,如降血脂、抗血栓性心脑血管、预防和治疗高血压、动脉粥样硬化,增强人体的免疫功能,还具有抗肿瘤、抗脂质过氧化、抑制溃疡和增强胰岛素和减肥等方面的作用[董杰明等,2003,卫生研究,32(3):299-301]。尤其是在糖尿病、心血管疾病及癌症方面的医疗价值,γ-亚麻酸已成为学术界研究的热点。
Δ6-脂肪酸脱氢酶能特异性催化亚油酸(linoleic acid, C18:2Δ9,12)和α-亚麻酸 (α-linolenic acid, C18:3Δ9,12,15) 羧基端的第6和第7位碳原子之间***一个新的双键,分别脱氢形成 γ-亚麻酸 (γ-linolenic acid, C18:3Δ6,9,12)和十八碳四烯酸 (stearidonic acid, C18:4Δ6,9,12,15),它们再通过碳链延伸和脱氢进一步形成其它长链的多不饱和脂肪酸(long-chain polyunsaturated fatty acid, LC-PUFAs),因此Δ6-脂肪酸脱氢酶是人和哺乳动物体内合成长链多不饱和脂肪酸的关键酶。这些长链多不饱和脂肪酸是机体组织生物膜组成成分,起到维持细胞正常功能和增加机体抗逆性的作用[Napier JA et al,1999,Curr.Opin.Plant Biol,2:123-127],同时也是***素、环***素和白三烯类等具有强烈生理活性的自身调节物的前体[Horrobinn DF,1992,Prog Lipid Res.,31:163-194]。Δ6-脂肪酸脱氢酶活性的降低将导致γ-亚麻酸的合成量减少,引起人体的各种机能紊乱,进而引发各种疾病。因此,从不同生物体中克隆Δ6-脂肪酸脱氢酶基因,再与不同表达载体连接后转入不同的宿主细胞进行表达,利用宿主产生γ-亚麻酸和其他长链多不饱和脂肪酸具有极大应用前景。
由于人们越来越认识到γ-亚麻酸和其他长链多不饱和脂肪酸的重要性,因此将注意力又转向对Δ6-脂肪酸脱氢酶的研究上。Δ6-脂肪酸脱氢酶属于一类膜整合酶,由于分离和鉴定膜结合蛋白的难度很大[MaKeon,1981,酶学方法,12141-12147;wang等,1988,植物生理学生物化学,26:777-792],因此常规的生物化学方法很难得到包括Δ6-脂肪酸脱氢酶在内的各种膜结合蛋白性质脱氢酶高级机构,而只能通过对酶的核苷酸序列进行初步研究,对于Δ6-脂肪酸脱氢酶的生物学功能验证,许多实验室采用了从各种生物体中克隆相关的基因并转入各种受体细胞中,然后在受体细胞中观察其脂肪酸改变的方法。序列对比的结果表明,编码Δ6-脂肪酸脱氢酶的核苷酸序列具有共同的机构特性:存在三个组氨酸保守区,形成四次跨膜的结构[Kyte et al,1982,J.Mol.Biol.157:105-132],此外,除了蓝细菌外,真核生物的Δ6-脂肪酸脱氢酶的氨基端都含有类似于细胞色素b5(Cytb5)血红素结合区(HPGG)[Napier JA,Sayanova O,Stobart AK,et al.,1997,Biochem.J.,157:105-132],这些都是维持脱氢酶活性所必须的。
目前,通过多种分子生物学方法已从动物、植物、微生物等不同来源中分离到许多Δ6-脂肪酸脱氢酶基因的同源序列,并且证明具有相应的生物学功能,然而,尽管获得了很多Δ6-脂肪酸脱氢酶的基因序列,但是在酶的纯化方面存在的技术困难,目前仍没有从酶水平揭示其在自然环境中的生化特性。因此,只能借助于发掘更多的不同来源的Δ6-脂肪酸脱氢酶基因序列,通过基因序列分析来更深入揭示Δ6-脂肪酸脱氢酶的生物学功能,并为将来酶的纯化和生化特性的揭示以及进一步的应用打下基础。此外,这些不同来源分离到的脱氢酶基因催化活性较低且大多数对脂肪酸底物链长、双键数目及双键位置不具有严格的专一性,除目标产物外,还会生产一些非特异脂肪酸。因此,需要继续筛选具有高的底物特异性的Δ6-脂肪酸脱氢酶基因,并应用基因工程技术构建特异性生产多不饱和脂肪酸的转基因油料植物,直接改善油脂品质,更加具有实际应用价值。本研究通过多种手段发掘多不饱和脂肪酸合成的高效、特异性新基因,为新一代转基因脂肪酸产品的品质改良奠定基础。
发明内容
本发明的一个目的是提供一种从深黄被孢霉(Mortierella isabellina)M6-22中分离得到的Δ6-脂肪酸脱氢酶基因及该基因编码的氨基酸,该基因核苷酸序列或核苷酸序列的片段如SEQ ID NO:1所示,或与SEQ ID NO:1互补的核苷酸序列,该基因序列长为1515bp(碱基),其中1-1515为编码Δ6-脂肪酸脱氢酶成熟多肽的开放阅读框;该基因编码的氨基酸序列如SEQ ID NO:2所示的多肽或其片段。
本发明另一目的是提供一种含有Δ6-脂肪酸脱氢酶基因的重组表达载体,是将SEQ ID NO:1所示基因直接与不同表达载体(质粒、病毒或运载体)连接所构建的重组载体。
可用本领域的技术人员熟知的方法来构建含编码来源于深黄被孢霉M6-22的Δ6-脂肪酸脱氢酶的核苷酸序列和合适的转录/翻译调控元件的表达载体。这些方法包括体外重组DNA技术、DNA合成技术、体内重组技术等[Sambroook,et al, Molecular Cloning, a Laboratory Manual, Cold Spring Harbor Laboratory, New York, 1989]。所述的编码深黄被孢霉M6-22 Δ6-脂肪酸脱氢酶的核苷酸序列可有效连接到表达载体的恰当启动子上,以指导mRNA合成。这些启动子的代表性例子有:大肠杆菌的lac或trp启动子;λ噬菌体的PL启动子;真核启动子包括CMV早期启动子、HSV胸苷激酶启动子、早期和晚期SV40启动子、反转录病毒的LTRs和其它一些已知的可控制基因在原核细胞或真核细胞或其病毒中表达的启动子。表达载体还包括翻译起始用的核糖体结合位点和转录终止子等。在载体中***增强子序列将会使其在高等真核细胞中的转录得到增强。增强子是DNA表达的顺式作用因子,通常大约有10-300bp,作用于启动子以增强基因的转录,如腺病毒增强子。
本发明另一目的是提供一种含有Δ6-脂肪酸脱氢酶基因或上述重组表达载体的宿主细胞,该细胞是细菌细胞、真菌细胞、植物细胞或动物细胞,或这些宿主细胞的后代,宿主细胞的代表性例子有:大肠杆菌;真菌细胞或酵母;植物细胞如油菜、烟草、大豆;昆虫细胞如果蝇S2或Sf9;动物细胞如CHO、COS或Bowes黑素瘤细胞等。
用本发明所述的核苷酸序列或含有核苷酸序列的重组载体优化宿主细胞可用本领域的技术人员熟知的方法进行。当宿主为原核生物如大肠杆菌时,能吸收DNA的感受态细胞可在指数生长期收集菌体,用CaCl2、电穿孔等方法进行。当宿主是真核生物,可选用DNA转染法。显微注射、电穿孔、脂质体包装等方法。
本发明的核苷酸序列是DNA形式的,DNA形式包括cDNA、基因组DNA或人工合成的DNA,DNA可以是单链的或是双链的,编码成熟多肽的编码区序列可以与SEQ ID NO:2所示的编码区序列相同或是简并的变异体。
本发明还包括编码从深黄被孢霉M6-22获得的Δ6-脂肪酸脱氢酶的核苷酸序列的片段。如本发明所用,术语“片段”是指能编码基本上保持本发明天然的相同的生物学功能或活性的多肽的核苷酸序列。通过本文的阐述,这样的片段、被认为在本领域技术人员的知识范围之内。
本发明中的多肽和核苷酸序列优选以分离的形式提供,更佳地被纯化至均质。
本发明中特异核苷酸序列能用多种方法获得。例如,用本领域熟知的杂交技术分离核苷酸序列。这些技术包括但不局限于:(1)用探针与基因组或cDNA文库杂交以检出同源的核苷酸序列;和(2)表达文库的抗性筛选以检出具有共同结构特征的克隆的核苷酸序列片段。
本发明的DNA片段序列也能用下列方法获得:(1)从基因组DNA分离双链DNA序列;(2)化学合成DNA序列以获得所述多肽的双链DNA。
上述提到的方法中,分离基因组DNA最不常用。DNA序列的直接化学合成法是经常选用的方法。更经常选用的方法是DNA序列的分离。分离感兴趣的cDNA的标准方法是从高表达该基因的供体细胞分离mRNA并进行转录,形成质粒或噬菌体cDNA文库。提取mRNA的方法已有多种成熟的技术,用试剂盒也可从商业途径获得。而构建cDNA文库也是通常的方法。当结合聚合酶链式反应技术(PCR)时,即使极少的表达产物也能克隆。
本发明提供的核苷酸序列是一种高效的特异性的脂肪酸脱氢酶,可以将其与载体连接后转化至微生物细胞体内生产不饱和脂肪酸,具有产物特异性高、生产周期短、生产不受场地、气候、季节的影响及利用不同的菌种和培养基适合开发功能油脂等优点,可以用于商业化生产,直接改善油脂品质,更加具有实际应用价值。本发明应用基因工程技术构建特异性生产多不饱和脂肪酸的转基因酵母细胞生产不饱和脂肪酸,具有操作简单、成本低、可行性高等优点,为新一代转基因脂肪酸产品的品质改良奠定基础。
附图说明
图1为本发明的深黄被孢霉M6-22的Δ6-脂肪酸脱氢酶和鲁氏毛霉Δ6-脂肪酸脱氢酶的氨基酸序列同源性比较图;其中MID6-1为本发明的深黄被孢霉M6-22Δ6-脂肪酸脱氢酶,MRD6为鲁氏毛霉Δ6-脂肪酸脱氢酶,Consensus为两序列之间相同的氨基酸序列;
图2为本发明所构建的酿酒酵母表达载体pY3MID6-1;
图3为本发明含pYES3/CT空载体的转基因酵母的气相色谱图;
图4为本发明含重组质粒pY3MID6-1的转基因酵母的气相色谱图。
具体实施方式
下面结合附图和实施例对本发明作进一步详细说明,但本发明保护范围不局限于所述内容,实施例中使用的试剂和方法,如无特殊说明,均采用常规试剂和使用常规方法。
实施例1:从深黄被孢霉M6-22中分离Δ6-脂肪酸脱氢酶的核苷酸序列
根据深黄被孢霉M6-22的RNAseq分析结果,发现一条编码Δ6-脂肪酸脱氢酶的mRNA序列,进一步分析获得一段编码完整蛋白质的编码序列,并根据编码序列设计合成特异性引物(引物1和引物2)。同时将深黄被孢霉M6-22接种到PDA液体培养基中,28℃培养48h,收集菌丝体,用液氮研磨成菌丝粉,然后采用真核细胞总RNA提取试剂盒(Promega公司产品)提取深黄被孢霉M6-22的总RNA,再利用反转录试剂盒(fermentas公司产品)反转录合成第一条cDNA,以此cDNA为模板,用引物1和引物2进行PCR反应,反应所用组份和扩增条件如下:
引物1:MID6-1F1:5`-ATGCCTCCTAACAATAGGGCTATCGA-3`
引物2:MID6-1R1:5`-TCACGCATGAGGTGCTACCATCTCT-3`;
PCR扩增体系(25 μL)组成如下:
10×Ex Taq Buffer 2.5 μL
dNTP(2.5 μmol/L) 2 μL
模板 3 μL
MID6-1F1(10 μmol/L) 2 μL
MID6-1R1(10 μmol/L) 2 μL
Ex Taq DNA polymerase(5U/μL) 2 μL
无菌ddH2O 补足至25 μL
扩增条件:94℃变性4min,再用94℃ 1min、58℃ 1min、72℃ 2min进行30个循环,扩增产物按照部分序列扩增中方法连接到pMD18-T载体中,验证正确后送出测序。结果显示所扩增得到的片段大小为1515bp,通过其编码的氨基酸序列在Genebank数据库中用Blast(Basic Local Alignment Search Tool)程序进行同源检索,检索结果表明与该片段最相似的同源片段为Δ6-脂肪酸脱氢酶,但并不完全相同,证明所扩增的片段为新的潜在的脱氢酶基因的部分片段。
实施例2:所分离核苷酸序列的同源性搜索
将推测的Δ6-脂肪酸脱氢酶的氨基酸序列在Genbank上进行同源性搜索,所得同源序列大部分为编码Δ6-脂肪酸脱氢酶的序列,少数为假定蛋白的序列,选择已做功能验证的Δ6-脂肪酸脱氢酶做同源性比较,其中与鲁氏毛霉(Mucor rouxii)的Δ6-脂肪酸脱氢酶(AF290983_1)相似性最高,为56%。(图1, MID6-1为本发明的深黄被孢霉M6-22Δ6-脂肪酸脱氢酶,MRD6为鲁氏毛霉Δ6-脂肪酸脱氢酶,Consensus为两序列之间相同的氨基酸序列,这说明本发明提供的核苷酸序列所编码的酶为潜在新的Δ6-脂肪酸脱氢酶。
实施例3: 酿酒酵母重组表达载体的构建
根据SEQ ID NO:1所示编码区序列,设计出一对基因特异性扩增引物(引物3和引物4):
引物3:MID6-1F2:5`-CGGGATCCATGCCTCCTAACAATAGGGCTA-3`
引物4:MID6-1R2:5`-ATGCGGCCGCTCACGCATGAGGTGCTACCATC-3`
此两个引物的5‵端下划线部分分别含有BamHⅠ和NotⅠ 酶切位点,所用的扩增条件和反应组分和以cDNA为模板的PCR反应相同,扩增产物的测序结果显示和SEQ ID NO:1所示1-1515bp的序列一致;然后取25ul PCR产物和10ul pYES3/CT(Invitrogen公司)分别进行双酶切,电泳回收酶切大片段,并用T4连接酶在16℃连接4h,连接产物转化大肠杆菌HD5α,通过质粒提取和PCR筛选阳性克隆,并进行测序鉴定,质粒构建结果见图2,所构建的含有Δ6-脂肪酸脱氢酶基因的表达载体命名为pY3MID6-1。
实施例4:酿酒酵母重组表达载体和空载体转化酿酒酵母细胞
挑取酿酒酵母菌株INVSc1单菌落于5ml YEPD液体培养基中,30℃摇床过夜培养,按1%的接种量转接于100ml的YEPD液体培养基中,30℃摇床摇至OD600于1.3-1.5之间;4℃、4000g离心5min收集沉淀细胞,用100ml预冷的无菌ddH2O洗涤细胞,4℃、4000g离心5min收集沉淀细胞,再用50ml预冷的无菌ddH2O洗涤细胞,4℃、4000g离心5min收集沉淀细胞,用20ml预冷的1M山梨醇洗涤细胞,4℃、4000g离心5min收集沉淀细胞,细胞用0.5ml的预冷的1M山梨醇悬浮,每80ul分装于1.5ml预冷的离心管中,取1ug线性化的重组表达载体pY3MID6-1和空载体pYES3/CT分别加入到80ul的感受态细胞中,混匀后转至0.2cm的电转杯中,冰上孵育5min,转入电转仪中电击(电击条件:电压1.5kV,电容25uF,电阻200Ω,电击时间为4-10ms),电击完毕后立即加入1ml 1M预冷的山梨醇并吹匀,30℃孵育2h后分别涂布于SC-Trp(无色氨酸)选择培养基上,置30℃培养3-4天。
实施例5: 酵母工程菌的诱导表达与脂肪酸甲酯的气相色谱分析
挑取分别转化了重组表达载体pY3MID6-1和空载体pYES3/CT并在SC-Trp选择培养基(色氨酸合成缺陷型培养基)平板上出现的阳性转化子,分别接种于15ml 液体SC-Trp选择培养基(含2%葡萄糖),30℃摇菌培养24h,转接于100ml的SC-Trp选择培养基(含2%的半乳糖和1%的棉子糖)中,使其初始OD600为0.4,加入0.5mmol /L的外源底物亚油酸,30℃继续振荡培养72h,4000g离心收集菌体,用去离子水洗涤三次,菌体于50℃烘干,研碎,取100mg干菌体粉末加入5ml 5%的KOH-CH3OH溶液中,70℃反应3h,反应结束后冷却至室温,用6M的盐酸调节溶液的pH值到2.0,加入4ml 14%BF3-CH3OH,70℃反应1.5h,合成脂肪酸甲酯;再加入10ml饱和的NaCl溶液,剧烈震荡混匀,转移至分液漏斗中,用8ml 1:4的氯仿:环己烷抽提两次,合并两次的提取液,把含有脂肪酸甲酯的溶剂用氮气吹干,用200ul的正己烷回溶样品,最后用0.45um微孔滤膜过滤除去大颗粒杂质。
实施例6: 脂肪酸气相色谱分析
采用气相色谱分析仪器分析转基因酵母工程菌的诱导表达情况,气相色谱分析仪器为岛津GC-7A,柱子:弹性石英毛细管柱,0.32×30m,固相支持物:聚二乙二醇丁二酸酯镀膜物:聚酰亚胺。载气:N2,线速10cm/s。分流比:100:1,气化室温度:250℃,柱温:180℃,尾吹:50ml/min,检测器:氢火焰离子化检测器。把上述制备的脂肪酸甲酯化样品进行GC分析,上样量为1ul;分析软件:Anstar。
色谱分析结果见图3、4,图3显示含pYES3/CT空载体的转基因酵母,图4显示含重组质粒pY3MID6-1的转基因酵母;与图3相比,图4中保留时间为15.05min对应的峰与γ-亚麻酸甲酯标准品一致,即为深黄被孢霉M6-22Δ6-脂肪酸脱氢酶催化亚油酸产生的γ-亚麻酸。
序列表
序列表
<110> 昆明理工大学
<120> 一种Δ6-脂肪酸脱氢酶基因及其应用
<160> 6
<170> PatentIn version 3.5
<210> 1
<211> 1515
<212> DNA
<213> 深黄被孢霉M6-22
<400> 1
atgcctccta acaatagggc tatcgagccc actttataca aatacatcac gcagaaagag 60
ctgagtgatc gtgttaaaca aggagaggtt ctgatcatct atgacaacaa agtgtacaag 120
ctagatcgct ggatcaagtc ccatcctggt ggtgagctag ctatccgcca cgctgtagga 180
aaagatgcca cagacgagat cactgctatg catccaccac atgtatacca aaaatccatt 240
cgtccatttt atgtgggtga atatgtggaa aatatacttc acatgccaaa aactcaggca 300
ccactagcca gccacgcccc cactaccagc aataaccaaa tcgatgtaga caagtcccaa 360
tctattatca cacggttata caatgaccat atgaaagtga tccaagaaca aaaggcacgg 420
cctcaagcgg atatacaaac agtgcgtttc cactatcagc gattagagaa tgaaatccgt 480
tcacgaggtc tcatgaagtg caattactgg aagtatggca aagaatgctg tcgttatgtc 540
ttgttcattt accttgcggt ctatctgatc ctcaagggaa cgcaaacttg gcattatatg 600
ttgagtgccg tgtttatggc atgtttctgg catcagctta cattcaccgc tcatgatgct 660
ggtcacaacg gtataacagg aaaataccat atagatcacc ttataggcat attcattgcc 720
gatttccttg gtggcctttc cataggttgg tggaagaaca atcacaacgt ccatcatatt 780
gttaccaatg accctgctca cgatccggat attcagcata tgcccttttt tgccatcact 840
acccgcatct tcaacaccta ttcgagctat taccaccgcg tcatgaaatt ggatgccgcc 900
gccaaattct ttgttcgtca tcagcacaag ctttattata ttattttatc gcttggaagg 960
ttcaaccttc ataatttgag ctttgttttc ttgttcactg ctccacgtgt caaataccga 1020
tggttggaaa tctttggtat ttgtgtgttc tttacctggt attcctacct gttgtctttc 1080
ctaccgtctg cttcgatcat attcgcctac gttcttattt cttacacatt gactgtcccg 1140
ttgcacattc aaatcactct atcccatttc ggtatgtcta ctgaggatct aggacctaac 1200
gagcctttcg cagctaaaca gcttcgtacc accatggatg tcgactgccc tgaatggttt 1260
gactggttcc atggaggact tcagtaccaa gctgtacatc atttgttccc tcgcatccca 1320
agacacaatt tgcgacaatg tgtgcctttg gtcaggcagt tctgtaaaca gctcggtctc 1380
gagtaccact gttatacctt ttccaagggc aatggcgtgg tactaggtgg actcaaggct 1440
gtaggtgatc aacttcgcct tatcgacgaa gttgccaagc ataatgccga agagatggta 1500
gcacctcatg cgtga 1515
<210> 2
<211> 504
<212> PRT
<213> 深黄被孢霉M6-22
<400> 2
MET Pro Pro Asn Asn Arg Ala Ile Glu Pro Thr Leu Tyr Lys Tyr
1 10
Ile Thr Gln Lys Glu Leu Ser Asp Arg Val Lys Gln Gly Glu Val
20 30
Leu Ile Ile Tyr Asp Asn Lys Val Tyr Lys Leu Asp Arg Trp Ile
40
Lys Ser His Pro Gly Gly Glu Leu Ala Ile Arg His Ala Val Gly
50 60
Lys Asp Ala Thr Asp Glu Ile Thr Ala MET His Pro Pro His Val
70
Tyr Gln Lys Ser Ile Arg Pro Phe Tyr Val Gly Glu Tyr Val Glu
80 90
Asn Ile Leu His MET Pro Lys Thr Gln Ala Pro Leu Ala Ser His
100
Ala Pro Thr Thr Ser Asn Asn Gln Ile Asp Val Asp Lys Ser Gln
110 120
Ser Ile Ile Thr Arg Leu Tyr Asn Asp His MET Lys Val Ile Gln
130
Glu Gln Lys Ala Arg Pro Gln Ala Asp Ile Gln Thr Val Arg Phe
140 150
His Tyr Gln Arg Leu Glu Asn Glu Ile Arg Ser Arg Gly Leu MET
160
Lys Cys Asn Tyr Trp Lys Tyr Gly Lys Glu Cys Cys Arg Tyr Val
170 180
Leu Phe Ile Tyr Leu Ala Val Tyr Leu Ile Leu Lys Gly Thr Gln
190
Thr Trp His Tyr MET Leu Ser Ala Val Phe MET Ala Cys Phe Trp
200 210
His Gln Leu Thr Phe Thr Ala His Asp Ala Gly His Asn Gly Ile
220
Thr Gly Lys Tyr His Ile Asp His Leu Ile Gly Ile Phe Ile Ala
230 240
Asp Phe Leu Gly Gly Leu Ser Ile Gly Trp Trp Lys Asn Asn His
250
Asn Val His His Ile Val Thr Asn Asp Pro Ala His Asp Pro Asp
260 270
Ile Gln His MET Pro Phe Phe Ala Ile Thr Thr Arg Ile Phe Asn
280
Thr Tyr Ser Ser Tyr Tyr His Arg Val MET Lys Leu Asp Ala Ala
290 300
Ala Lys Phe Phe Val Arg His Gln His Lys Leu Tyr Tyr Ile Ile
310
Leu Ser Leu Gly Arg Phe Asn Leu His Asn Leu Ser Phe Val Phe
320 330
Leu Phe Thr Ala Pro Arg Val Lys Tyr Arg Trp Leu Glu Ile Phe
340
Gly Ile Cys Val Phe Phe Thr Trp Tyr Ser Tyr Leu Leu Ser Phe
350 360
Leu Pro Ser Ala Ser Ile Ile Phe Ala Tyr Val Leu Ile Ser Tyr
370
Thr Leu Thr Val Pro Leu His Ile Gln Ile Thr Leu Ser His Phe
380 390
Gly MET Ser Thr Glu Asp Leu Gly Pro Asn Glu Pro Phe Ala Ala
400
Lys Gln Leu Arg Thr Thr MET Asp Val Asp Cys Pro Glu Trp Phe
410 420
Asp Trp Phe His Gly Gly Leu Gln Tyr Gln Ala Val His His Leu
430
Phe Pro Arg Ile Pro Arg His Asn Leu Arg Gln Cys Val Pro Leu
440 450
Val Arg Gln Phe Cys Lys Gln Leu Gly Leu Glu Tyr His Cys Tyr
460
Thr Phe Ser Lys Gly Asn Gly Val Val Leu Gly Gly Leu Lys Ala
470 480
Val Gly Asp Gln Leu Arg Leu Ile Asp Glu Val Ala Lys His Asn
490
Ala Glu Glu MET Val Ala Pro His Ala ***
500
<210> 3
<211> 26
<212> DNA
<213> 人工序列
<400> 3
atgcctccta acaatagggc tatcga 26
<210> 4
<211> 25
<212> DNA
<213> 人工序列
<400> 4
tcacgcatga ggtgctacca tctct 25
<210> 5
<211> 30
<212> DNA
<213> 人工序列
<400> 5
cgggatccat gcctcctaac aatagggcta 30
<210> 6
<211> 32
<212> DNA
<213> 人工序列
<400> 6
atgcggccgc tcacgcatga ggtgctacca tc 32
Claims (3)
1.一种Δ6-脂肪酸脱氢酶基因,其核苷酸序列如SEQ ID NO:1所示,编码如SEQ ID NO:2所示的氨基酸序列。
2.一种宿主细胞,所述宿主细胞含有权利要求1所述的深黄被孢霉Δ6-脂肪酸脱氢酶基因。
3.权利要求1所述的Δ6-脂肪酸脱氢酶基因在生产多不饱和脂肪酸中的应用。
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