5类有毒动物毒液金属蛋白酶研究进展

徐志文，任雪敏，吴朝妍，雷 林

5类有毒动物毒液金属蛋白酶研究进展

徐志文1，任雪敏2*，吴朝妍3，雷 林1

（1. 遵义市林业局，贵州 遵义 563000；2. 遵义市林业科学研究所，贵州 遵义 563000；3. 西南林业大学 云南省森林灾害预警与重点实验室，云南 昆明 650224）

金属蛋白酶普遍存在于动物、植物及细菌等生物体中。金属蛋白酶被保留在蛇、蝎子、寄生蜂、水母及蜘蛛的毒液中，参与生理学过程，在其捕食、防御及消化等过程中发挥着重要作用。文章归纳了金属蛋白酶家族分类，截至目前分为17组74个家族，阐述了这5类携毒动物毒液金属蛋白酶在序列结构、家族分类、生物活性、功能机制等方面的研究，发现M10家族金属蛋白酶存在于寄生蜂和水母毒液中，M13家族金属蛋白酶存在于寄生蜂和蝎子毒液中，M12家族金属蛋白酶普遍存在于蛇、寄生蜂、蝎子、水母毒液中。蛇毒液金属蛋白酶研究相对深入和全面，其具有降解细胞外基质蛋白、调控细胞、抑制血小板聚集等活性及功能。在蝎子、寄生蜂、蜘蛛及水母中的毒液金属蛋白酶研究相对较少，其分子结构、功能及作用机制等尚不明晰。本研究将加深学者对毒液金属蛋白酶的认识，并为毒液金属蛋白酶今后的研究方向和应用提供参考。

毒液金属蛋白酶；家族分类；生物活性；功能机制；研究

金属蛋白酶是生物体内行使功能的主要蛋白酶成分之一，在动植物及微生物的发育调控、免疫应答及非生物逆境胁迫响应等生理学过程中发挥着重要作用。金属蛋白酶是包含金属小肽和大分子金属蛋白的一类蛋白酶，其活性主要是依赖一种或多种金属离子，是能够催化肽类和蛋白质中肽键水解的一类蛋白酶。在蛇、蜘蛛、蝎子、寄生蜂及水母这5类携毒动物的毒液或毒素中也保守存在，有趣的是金属蛋白酶作为这5类携毒动物毒液或毒素蛋白的主要组成成分[1-6]，在其捕食及消化等过程中发挥重要作用。本文从金属蛋白酶的结构及家族分类，其在蛇、蝎子、寄生蜂、蜘蛛及水母5类动物毒液中的研究进展进行综述，为后期毒液金属蛋白酶研究方向和应用提供参考。

1 金属蛋白酶的结构及家族分类

根据酶的催化位点类型将金属蛋白酶划分为32个家族（M1-M33，未见M21），一半的家族含有与金属离子捆绑的“His-Glu-Xaa-Xaa-His”（或者“HEXXH”）五肽结构，另一半家族的金属离子不与五肽结构捆绑[7]。该五肽“HEXXH”的共识序列能被更精确的定义为“abXHEbbHbc”，其中b是不带电荷的残基、c是疏水性的残基、X几乎可以是任何氨基酸[8]。32个家族的金属蛋白酶被分为5个超家族，第一超家族（gluzincin, MA）含有捆绑金属离子的“HEXXH+E”形式的催化结构域，该组别含有M1（membrane alanyl）、M2（peptidyl-dipeptidase）、M4（thermolysin）、M5（mycolysin）和M13（neprilysin）共5个家族。第二超家族（metzincin, MB）含有捆绑金属离子的“HEXXH+H”形式的催化结构域，该组别含有M12（astacin，包括astacin和reprolysin亚家族）、M10（interstitial collagenase，包括serralysin和matrixin亚家族）、M11（Autolysin）和M7（streptomyces small neutral protease）共4个家族。第三超家族（other metallopeptidase with “HEXXH” motif）含有捆绑未知金属离子“HEXXH+E”形式的催化结构域，该组别含有M3（thimet oligopeptidase）、M6（immune inhibitor A）、M8（leishmanolysin）、M9（vibrio collagenase）、M26（IgA-specific metalloendopeptidase）、M27（tetanus toxin）、M30（staphylococcus neutral protease）、M31（clostridial collagenase）、M32（carboxypeptidase Taq）等9个家族。第四超家族（other metallopeptidases with known metal ligands）是所捆绑金属离子结合在“HEXXH”以外的区域，该组别含有M14（carboxypeptidase A）、M15（zinc D-Ala-D-Ala carboxypeptidase）、M16（pitrilysin）、M17（leucyl aminopeptidase）、M24（methionyl aminopeptidase）等5个家族。第五超家族（metallopeptidases with unknown metal ligands）捆绑的金属离子配体、氨基酸及位置是完全未知的，该组别含有M18（yeast aminopeptidase I）、M19（membrane dipeptidase）、M20（glutamate carboxypeptidase）、M22（O-Sialoglycoprotein endopeptidase）、M23（β-lytic endopeptidase）、M25（X-His-dipeptidase）、M28（vibrio leucyl aminopeptidase）、M29（thermophilic aminopeptidase）、M33（aminopeptidase Y）等9个家族[7]。Rawling等[9]基于一级结构和序列同源性将所有金属蛋白酶分为MA、MC、MD和ME等17个组，17个组细化为M1、M2和M3等74个家族组成，但该分类未见用于毒液金属蛋白酶的研究。

基于金属蛋白酶的家族分类情况，研究者可将蛇、蜘蛛、蝎子、寄生蜂及水母5类携毒动物毒液中发现的金属蛋白酶进行分类。蛇、蝎子、蜘蛛及寄生蜂中普遍发现的毒液金属蛋白酶属于Metzincin（MB）组中的M12家族[10-12]，少数几种蝎子和寄生蜂毒液金属蛋白酶属于Gluzincin（MA）组中的M13家族[1]，极少数寄生蜂毒液金属蛋白酶属于M10家族[13]，水母刺细胞中发现M10和M12家族的毒液金属蛋白酶[14]。

2 5类携毒动物毒液金属蛋白酶

2.1 蛇毒液金属蛋白酶

金属蛋白酶广泛存在于蛇毒液中，其单一序列结构、酶活特性及功能等在蛇毒液研究中较为深入。它们属于MA组中的M12家族，Reprolysin成员。蛇毒液中的金属蛋白酶（snake venom metalloproteinases, SVMPs）根据其功能活性、核酸序列及结构域可分为4类：P-I型，只含有1个金属蛋白酶结构域（metalloproteinase domain，M）；P-II型，含有P-I型的金属蛋白酶结构域和一个去整合素结构域（disintegrin domain，D）；P-III型，包含3个结构域，在P-II型基础上再加一个富半胱氨酸结构域（cysteine-rich domain，C）；P-IV型，在P-III型的基础上，其富含半胱氨酸结构域末端再连接捆绑有二硫键的凝集素样结构域（lectin-like domains）[10,15]。但在2008年，有研究[16]以蛇毒液金属蛋白酶的mRNA序列和蛋白质结构为依据，重新将P-IV型SVMPs归为P-III型。目前，SVMPs主要分为3个类型：P-I型（Ia）、P-II型（IIa、IIb、IIc、IId）、P-III型（IIIa、IIIb、IIIc、IIId）[17]。P-I型、P-II型和P-III型的分子量大小不一，P-I型的分子量一般介于20～30 kDa，P-II型的分子量范围一般为30～60 ku，P-III型的分子量一般介于60～100 ku[2]，但仅以分子量大小来判断其家族归属类型是不准确的。

SVMPs可降解细胞外基质蛋白（extracellular matrix proteins，ECM），溶解基底膜中的胶原蛋白（collagen）、弹性蛋白（elastin）、层粘连蛋白（laminin）、明胶（gelatin）、纤维连接蛋白（fibronectin）、纤维蛋白原（fibrinogen）、巢蛋白（内功素，nidogen）和凝血酶敏感蛋白（thrombospondin）等组成成分[18-21]，对纤维蛋白原的降解能力最强。SVMPs可降解纤维蛋白原的α链和β链[22]，其中P-I SVMPs对α链水解性强[17,19]，P-II和P-III SVMPs对α和β链都具有较强水解活性[18]。蛇毒液金属蛋白酶具有溶纤维原、催化凝血酶原、激活凝血因子X、调控细胞、抑制血小板聚集、促发炎、灭活丝氨酸蛋白酶抑制剂等活性及功能[2,23-31]，使咬伤的动物体出现内部凝血系统受损、血栓形成、细胞凋亡、血管坏死等发生，外部出现组织受损、炎症、水肿及出血等现象[20,32-34]。蛇毒液金属蛋白酶注入动物体最直接且肉眼可见的影响是导致出血和水肿[10,35]，绝大部分的P-II SVMPs和P-III SVMPs具强烈的出血活性，也有非出血性和促凝血的P-II和P-III SVMPs，如Berythractivase、Ecarin和HV1等[17,36-37]。对于Fibrolase、、Atroxase、ACLF和r ACLF等[38-41]绝大部分P-I SVMPs仅有蛋白水解活性，未曾展现出血效应或低出血效应，少部分P-I SVMPs具出血效应[42]。血小板聚集是作用于止血的复杂机制，SVMPs可以结合并切割血小板受体GPIbα和GPVI、血浆vWF受体，进一步溶解纤维蛋白原使血小板纤维原蛋白粘附受阻，从而影响血小板凝集功能[19,43-47]。

在探究蛇毒液金属蛋白酶功能时，发现SVMPs不仅可溶解血栓还可作用于癌细胞，有望开发成溶血栓剂和抗癌药物。SVMPs的溶纤维蛋白活性会影响血小板凝聚功能，抑制止血和血栓形成，因此可考虑作为溶血栓的潜在药物[19,45,47-48]。一种P-I SVMP rACLF能诱导宫颈癌细胞（hela cells）形态改变、分离和活性降低，但具体的机理还不清楚[38]。P-II SVMPs可能对肿瘤的转移有治疗潜力，这个过程需要细胞外基质与整联蛋白相互作用。有研究表明：P-II SVMPs可以阻止依赖RGD（arginine-glycine-aspartic acid，RGD）的αIIbβ3、α5β1、αVβ1、αVβ3等整联蛋白受体，参与肿瘤细胞的迁移和侵袭[49-50]。由于P-III SVMPs能裂解vWF，所以正在被开发成抗癌药物，如：Bothropoidin、Kaouthiagin、Jararhagin和Leucurogin等。含有93个氨基酸的Leucurogin对黑色素瘤细胞黏着、迁移、增值、转移、生长具有一定作用[51]；49 ku的P-IIIa SVMP Bothropoidin可诱导使细胞凋亡、迁移、粘附，抑制乳腺癌细胞和血管增生[52]；52 ku的P-IIIb SVMP Jararhagin可诱导细胞增加caspase-3通路，最终消减体内的肿瘤结节[33]。SVMPs作用于癌细胞的机制，可能是其包含的金属蛋白酶结构、去整合素结构和富含半胱氨酸去整合素结构能裂解ECM蛋白所致，而ECM蛋白决定着细胞的粘附等功能。

2.2 蝎子毒液金属蛋白酶

蝎子对人类生命健康造成严重威胁，非洲、中东、南美等热带地区每年有大量人被蝎子蜇伤，甚至致死。蝎子毒液由水、盐、脂质、毒素、氨基酸、多糖、核苷酸、多肽、蛋白质和其它未知化合物组成，蛋白质、肽酶、神经毒素是蝎毒毒性主要作用成分[6,53-55]。蝎子毒液中的透明质酸酶、丝氨酸蛋白酶、金属蛋白酶等酶，参与毒液注射并发挥重要作用[56-57]。金属蛋白酶作为主要成分被保留于蝎子毒液蛋白中，这些蛋白酶需要一个二价金属离子作为辅基，而具有蛋白水解活性[2,58]。最早，Fletcher等[59]在毒液中分离出一种命名为Antarease的纯化物可能是金属蛋白酶，对囊泡膜蛋白有裂解活性。目前，有研究揭示了、和等蝎子的毒液能够裂解强啡肽1-13（dynorphin 1-13），这种降解活性可能与金属蛋白酶有关[60-61]。可单一蝎子毒液金属蛋白酶的水解活性、功能及机制等仍不明晰[58,62-63]。

至2014年，研究者揭示了蝎子毒液水解纤维蛋白原的确与金属蛋白酶相关，且分析了分离纯化得到的金属蛋白酶的裂解位点[1]。值得注意的是，Carmo等[1]发现的毒液金属蛋白酶（TsMs1-9）与蛇、蜘蛛毒液金属蛋白酶同属于Metzincin超家族中的M12家族，而TsMs10与其家族分类不同，归类于Gluzincin超家族中的M13家族。也有研究者纯化鉴定到了一种与高血压相关的类血管紧张素转换酶（angiotensin-converting enzyme-like peptidase，ACE），该蛋白酶与金属蛋白酶具有较高的同源性[64]，属于M13家族。近些年，相继在、、和等蝎子[6,56,65-69]毒液中发现大量金属蛋白酶，仅有少部分研究通过直接纯化或蛋白表达来探索单一蝎子毒液金属蛋白酶的生物活性及功能[70]，现今关于蝎子毒液金属蛋白酶的生物活性、家族分类及功能机制等研究停滞不前，需填补很多空白来揭示和了解金属蛋白酶在蝎子毒液中扮演的角色。

2.3 蜘蛛毒液金属蛋白酶

有关蜘蛛毒液蛋白报道涉及平甲蛛属、狡蛛属、洞叶蛛属和寇蛛属等属，但平甲蛛属在世界上分布最广且造成咬伤卫生事件最多[71]。对平甲蛛属毒液蛋白研究也相对较早和较深入，在20世纪70和80年代就有研究者通过免疫组化技术、组织化学技术、凝胶电泳和分离等生物技术方法，在和等平甲蛛属蜘蛛毒液中发现存在蛋白酶[72-75]。首次发现蜘蛛毒液金属蛋白酶是在平甲蛛属的毒液中，被命名为Loxolysin A和Loxolysin B，Loxolysin A是一种能降解纤维连接蛋白和纤维蛋白原Aα和Bβ链、分子量为20～28 kDa的金属蛋白酶，Loxolysin B是一种具有降解明胶活性、分子量为32～35 kDa的金属蛋白酶[76]。随之，在、和等蜘蛛[77]毒液中相继发现金属蛋白酶存在，这些蜘蛛毒液金属蛋白酶具有水解胶原蛋白、纤维连接蛋白和纤维蛋白原等胞外基质蛋白的活性。但都未得到金属蛋白酶序列，且其表达特征、功能和家族归属一直未被论证。直到2007年，首次从毒液腺体的cDNA文库中鉴别出了一个类虾红素金属蛋白酶（astacin-like metalloprotease）序列，被定名为拥有Astacin家族标签的LALP[11]。类虾红素蛋白酶是Metzincin超家族M12家族中的成员，它有18个氨基酸形成催化结构域“–HEXXHXXGXX HEXXRXDR–”，其中3个组氨酸与锌结合的共识序列是必要的催化活性中心，金属活性位点含保守的甲硫氨酸残基被称为甲硫氨酸变区（MXY）[78-80]。Astacin家族成员被发现在多种生物体中，拥有多样而独特的生物学功能，在成熟生物体或胚胎的特定组织中表达[78,81-82]。而在动物毒液中存在未见有报道，研究首次揭示金属蛋白酶作为Astacin家族成员存在于蜘蛛毒液中，且LALP能够水解纤维蛋白和纤维连接蛋白，对兔内皮细胞有毒性[11]。但也有学者从蜘蛛毒液中鉴定出一种命名为Partitagin的金属蛋白酶，未阐述其所属家族，但有降解胞外基质活性和抑制血小板凝集功能[83-84]。

多个被命名为LALPs的虾红素样蛋白酶在平甲蛛属蜘蛛毒液中被鉴定到，其多种异构体在蜘蛛毒液中形成一个种内和种间毒素家族[85-87]。并且Astacins在和等蜘蛛毒液中高表达，表明虾红素样金属蛋白酶在平甲蛛属蜘蛛毒液中具有重要的生物学意义[85,87-89]。有研究发现，在平甲蛛属蜘蛛毒液中鉴定到的虾红素样金属蛋白酶具有降解胞外基质活性、溶纤维蛋白原、抑制血小板凝集等活性功能[71,86,90-91]。这些研究结果证实，在平甲蛛属蜘蛛毒液中被保守共有的M12家族类虾红素金属蛋白酶参与毒液注入生物体，发挥调节其他分子或直接参与捕猎、促进取食等重要功能[92]。

2.4 寄生蜂毒液金属蛋白酶

大量文献通过转录组和蛋白组等生物技术对蝶蛹金小蜂、管氏肿腿蜂、菜蛾盘绒茧蜂、颈双缘姬蜂、椰心叶甲啮小蜂等[93-97]寄生蜂毒液组成进行了分析，发现金属蛋白酶在其毒液器官中作为主要成分存在。研究者通过系统发育树和数据库Blast比对发现，寄生蜂毒液中存在的金属蛋白酶属于M10、M12和M13家族，被保守共有的绝大部分毒液金属蛋白酶属于M12家族，少部分为M13家族，M10家族极少[13]。目前，在绿长背泥蜂、阿尔蚜茧蜂、隆脊匙胸瘿蜂、波氏匙胸瘿蜂、短背茧蜂属、短背茧蜂属、椰心叶甲啮小蜂和管氏肿腿蜂等几种毒液中发现M13家族金属蛋白酶[93,98-101]，仅在中红侧沟茧蜂毒液中发现一个M10家族金属蛋白酶[13]，这两个家族的寄生蜂毒液金属蛋白酶活性、功能及机制都尚不明晰。

寄生蜂毒液中的M12家族金属蛋白酶被较早发现且普遍存在，但也仅有少部分研究揭示了其活性结构，在水解活性及功能机制等方面的研究仍匮乏。例如，寮黑瘤姬蜂毒液中分子量为39.9 kDa的Reprolysin金属蛋白酶，含有2个与锌结合的组氨酸残基保守催化结构域为HELGHVFSAPRD。由于其可能有特异性底物，普通底物不能检测到它的活性[102-103]。蜾蠃巨柄姬小蜂和栉角姬小蜂毒液金属蛋白酶的催化结构域为HELGHLLNxxHD[12]，丽蝇蛹集金小蜂毒液中的金属蛋白酶活性催化位点为HELGHNLGxxHD[104]，且Formesyn等[105]发现丽蝇蛹集金小蜂毒液金属蛋白酶对寄主细胞活性有影响。另外，在栉角姬小蜂毒液中发现3个金属蛋白酶基因（、、）编码的氨基酸序列与丽蝇蛹集金小蜂、蜾蠃巨柄姬小蜂和寮黑瘤姬蜂毒液金属蛋白酶氨基酸序列的相似性极高，且栉角姬小蜂毒液金属蛋白酶能阻碍寄主番茄叶蛾的生长发育[12]。之后很长一段时间未见有报道寄生蜂毒液金属蛋白酶蛋白活性及功能机制研究，最新的是Lin等[13]在中红侧沟茧蜂毒液中发现了一种调控寄主细胞包囊的金属蛋白酶，并阐释清楚该毒液金属蛋白酶是通过TOLL通路来行使功能的分子机制。以上这些报道的M12家族金属蛋白酶，在序列结构上与蛇毒液金属蛋白酶保守序列的同源性较高，其催化位点结构域的氨基酸残基组成都为“HEXGHXXGXXHD”形式。

2.5 水母毒素金属蛋白酶

水母类刺胞动物在捕猎和防御过程中，主要通过刺细胞内包含的大量毒素蛋白行使功能。但由于水母类刺胞动物的毒液难以收集，致使其毒液成分的研究相对其他携毒动物要滞后。在、、、、白色霞水母、、、沙海蜇、海蜇、等大量水母的研究报道中，发现金属蛋白酶在毒素提取物中占主要成分且发挥重要毒力作用[106-109]。其中沙海蜇中的毒液成分及毒液金属蛋白酶被研究的最多，发现其毒液中存在M10家族的基质金属蛋白酶和M12家族的类虾红素金属蛋白酶[14]。有研究者在沙海蜇中发现至少存在9个分子量为28～46 ku、57～83 ku和139 ku间的毒液金属蛋白酶[107]，且影响多种炎症因子表达增强炎症[110]。2021年，有研究者首次报道了沙海蜇毒液金属蛋白酶可直接降解基底膜成分来增加血管的通透性导致水肿[111]，其与毒素成分中的调节因子有协同效应，在调节亚基的激活下可水解偶氮酪蛋白，且首次在水母毒液中获得了3个与金属蛋白酶相关的多肽序列[112]。近期，有研究者发现沙海蜇毒液金属蛋白酶，与促使肌肉明显肿胀、增加血清中肌酸激酶（CK）和乳酸脱氢酶（LDH）含量、刺激肌肉组织炎症、破坏肌肉组织结构等相关[113]。以上都是通过粗毒液分离纯化的方法获得金属蛋白酶提取物，未通过序列的表达纯化获得单一的毒液金属蛋白酶。虽然水母毒液提取物中检测到金属蛋白酶存在，但它仍然是一类尚不清楚的金属蛋白酶。由于水母毒素量小、成分复杂且不稳定等原因，很难从水母毒液中纯化提取到单一的金属蛋白酶及完整序列，这限制了对其分子结构、家族分类、功能及作用机制等的研究。

3 小结与展望

本文概述了当前金属蛋白酶的家族分类，目前最新分为17组74个家族，但关于毒液金属蛋白酶家族研究普遍应用的是5个超家族32个家族的分类。毒液金属蛋白酶作为携毒动物中一类重要的水解酶，在蛇、蝎子、寄生蜂、水母及蜘蛛毒液中都发现存在大量金属蛋白酶，研究者对其序列结构、家族分类、生物活性、功能机制等的研究深度不一。通过对这5类携毒动物毒液金属蛋白酶家族归类的研究进行总结，发现M10家族金属蛋白酶存在于寄生蜂和水母毒液中，M13家族金属蛋白酶存在于寄生蜂和蝎子毒液中，M12家族金属蛋白酶普遍存在于蛇、寄生蜂、蝎子、水母毒液中。在蛇毒液中的金属蛋白酶活性、生物功能、家族归类及机制探究较为深入，具降解细胞外基质蛋白、催化凝血酶原、调控细胞、抑制血小板聚集、促发炎等活性及功能，且已经有不少种类的蛇毒液金属蛋白酶被应用到抗血栓、血清解毒、抗癌等医药领域。而在蝎子、寄生蜂、水母及蜘蛛4类动物毒液中的研究相对较少，特别是基于单一毒液金属蛋白酶核酸序列的研究。它在这4类动物毒液中扮演的角色引人思考，具体结构特征、活性功能和作用机制等亟待科研工作者深入探究。基于归纳的毒液金属蛋白酶在5类携毒动物中的研究现状，结合高通量测序、基因克隆、重组表达及蛋白互作等生物技术手段，将为毒液金属蛋白酶的研究及应用开拓思路。随着携毒动物毒液金属蛋白酶活性、功能及作用机理的不断挖掘，将在消炎、解毒、溶血栓、灭杀癌细胞等人类医药方面贡献重要作用。

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Research Progress on Venom Metalloproteinases of Five Types of Poison-carrying Animals

XU Zhiwen1, REN Xuemin2*, WU Chaoyan3, LEI Lin1

（1. Forestry Bureau of Zunyi, Zunyi, Guizhou 563000, China; 2. Zunyi Institute of Forestry Sciences, Zunyi, Guizhou 563000, China; 3. Key Laboratory of Forest Disaster Warning and Control of Yunnan Province, Southwest Forestry University, Kunming 650224, China）

Metalloproteinases are commonly found in organisms such as animals, plants and bacteria, and it is worth noting that metalloproteinases are retained in the venom of snakes, scorpions, parasitic wasps, jellyfishes, and spider, and participate in physiological processes, and play important roles in their predation, defense and digestion. This paper summarized the classification of metalloprotease families, which are divided into 74 families in 17 groups. Researches on the sequence structure, family classification, biological activity and functional mechanism of metalloproteinases of these five types of poison-carrying animals were comprehensively described. It was found that metalloproteases of M10 family existed in the venom of parasitic wasps and jellyfishes, that of M13 family existed in the venom of parasitic wasps and scorpions, M12 family were commonly found in the venom of snakes, parasitic wasps, scorpions and jellyfishes. Researches of snake venom metalloproteinases were relatively deep and comprehensive, which had the activities and functions of degrading extracellular matrix proteins, regulating cells, inhibiting platelet aggregation and so on. The studies of venom metalloproteinases in scorpions, parasitic wasps, spiders and jellyfishes were relatively less, and their molecular structure, family classification, function and mechanism of action, were still unclear. The article can deepen scholars' understanding of venom metalloproteinases, and provide references for the future research direction of venom metalloproteinases, and lay the foundation for the application of venom metalloproteinases.

venom metalloproteinases; family classification; bioactivity; functional mechanism; research

10.3969/j.issn.2095-3704.2023.04.79

Q955

A

2095-3704（2023）04-0538-11

2023-10-03

2023-10-16

贵州省林业科研项目（黔林科合J字[2022]30号）和中央引导地方科技发展资金项目（黔科中引地[2019]4004号）

徐志文（1992—），男，工程师，硕士，主要从事农林资源保护与利用研究，978115111@qq.com；*通信作者：任雪敏，工程师，硕士，1685800140@qq.com。

徐志文, 任雪敏, 吴朝妍, 等. 5类有毒动物毒液金属蛋白酶研究进展[J]. 生物灾害科学, 2023, 46(4): 538-548.