赭曲霉毒素A(ochratoxin A,OTA)主要由曲霉属(Aspergillus)和青霉属(Penicillium)真菌产生,是一类具有肾毒性、肝毒性、致畸性、神经毒性和遗传毒性的真菌毒素,已被国际癌症研究机构列为2B类潜在人类致癌物[1-2]。OTA产毒菌株种类繁多且无处不在。目前,已发现其对水果制品、谷物、咖啡豆、茶叶、草药、畜产品(肉、蛋、奶制品)等具有特殊的侵染力,可导致多种食品安全问题[3-4]。此外,畜禽摄入受OTA污染的饲料也可对其副产品造成间接污染[5]。据联合国粮农组织(Food and Agriculture Organization of the United Nations,FAO)报告(2010年),全世界每年约有25%的粮食作物受真菌毒素污染,其中2%的粮食因霉变而不能食用,可造成高达数十亿美元的经济损失和严重的粮食损耗问题[6]。因此,对OTA污染防控策略和生物合成途径的探索是解决食品安全问题和降低粮食损耗的关键环节之一。

OTA产毒菌株种类众多,已经被证实的导致食品和谷物污染的主要产毒真菌包括Aspergillus westerdijkiae(韦氏曲霉)、A. steynii、A. niger、A. welwitschiae、A. carbonarius、Penicillum nordicum和P. verrucosum等[3]。然而从很多报道中发现,OTA产毒菌的菌种分类存在混淆,早期Ciegler[7]和Hesseltine等[2]指出许多菌株可能是已知菌种的中间型[2,7]。而最为熟知的A. ochraceus(赭曲霉)中的一些分离株已被重新归类[8-10]。随着鉴定技术的发展,对OTA产毒菌种属的错误判断也不断地被更正。

OTA合成相关调控网络及遗传背景的不确定性也是导致其被错误判断的原因之一。通过对几种OTA产毒菌基因组序列进行分析,确定了一个OTA合成基因簇(otaA、otaB、otaC、otaD、otaR1和otaY),这些基因可编码OTA及其生物合成途径中的关键酶及其转录调控因子[11-12]。在早期,科学家们通过OTA的结构组成来预测其生物合成途径。当前,基于Huff等[13]、Harris等[14]和Gallo等[15-16]的研究成果,Wang等[12]和Ferrara等[17]对OTA生物合成途径进行了最新推测。明确OTA合成途径可能需要经历一个较长的过程,解决该问题将对后续制定OTA产毒菌防控策略提供坚实的理论基础。防控产毒真菌对食品、农作物的侵染以及对已经受OTA污染的谷物和食品进行脱毒处理,是切实减少粮食损耗,维护粮食安全亟须解决的重要课题。本研究将对OTA的产毒真菌种类、生物合成途径、调控基因以及OTA的防治策略进行系统分析,以期为OTA相关领域研究和制定相应的防治策略提供参考。

1 OTA的生物来源

OTA主要由曲霉属和青霉属中的一些菌株产生,其中曲霉属菌株大多数来自曲霉属环绕组(Aspergillus section Circumdati)、曲霉属黑色组(Aspergillus section Nigri)和曲霉属黄色组(Aspergillus section Flavi)3个曲霉群[3,18]。A. ochraceus(section Circumdati)是最早被鉴定的产OTA菌株[19],之后许多曲霉属和青霉属真菌被证实具备合成OTA的能力,如A. westerdijkiae、A. steynii、A. niger、P. verrucosum、P. nordicum等。

1.1 曲霉属中的OTA产毒菌

通过对曲霉属进行分类学评估,将section Circumdati分为Circumdati、Sclerotiorum和Steyniorum三类。该类群是造成农产品OTA污染的主要来源,也是被鉴定包含最多OTA产毒菌的曲霉群[20-23]。它们的来源多种多样,自从A. ochraceus第一次从高粱粒中发现后,又相继在咖啡、水稻等多种作物中发现,并一度被认为是世界范围内主要的OTA产毒菌株[19,24-25]。但从最近的报告来看,A. ochraceus被认为缺乏产生OTA的能力,已从比较基因组分析中发现其OTA典型生物合成簇存在缺失,其中的部分分离株已被重新鉴定为A. westerdijkiae[8-10, 26-28]。因此,可能很多菌株是被错误鉴定的。

目前,A. westerdijkiae和A. steynii是已知section Circumdati中最重要的OTA产毒菌[23]。A. westerdijkiae经常在热带地区被发现,其在系统发育上与A. ochraceus相似,但2种菌株菌核颜色有所不同,且前者不能在37 ℃下生长[8]。据报道,大约70%的A. westerdijkiae菌株能够产生OTA,而A. steynii占section Circumdati中产OTA菌株的90%,它们均可在污染土壤、谷物以及储存的食物中分离得到[9, 29-30]。目前,已将A. steynii和A. westerdijkiae视为必须防控的产OTA菌株。

Aspergillus section Nigri也包含重要的OTA产毒菌,通常被认为是有机酸和胞外酶的有效生产者[31]。据报道A. tubingensis是美国和意大利玉米中section Nigri的主要OTA产毒菌株[32]。A. nigri和A. carbonarii被证明是造成葡萄及其副产品中OTA污染的主要原因[33-34]。此外,A. welwitschiae也是section Nigri中重要的OTA产毒菌株之一[35]。而在Aspergillus section Flavi中,只有A. alliaceus (同A. albertensis)被报道产生OTA[35-36]。

1.2 青霉属中的OTA产毒菌

1969年,首次发现了产OTA的青霉属真菌P. verrucosum[37],但到目前为止,只有少数青霉属真菌被报道具备产生OTA的能力,如P. nordicum[38]、P. verrucosum[39]、P. brevicompactum、P. crustosum、P. olsonii、P. oxalicum[40]、P. thymicola[41]、P. chrysogenum,P. glycyrrhizacola和P. polonicum[42]。其中主要的OTA产毒菌有P. nordicum和P. verrucosum,也是目前被广泛认可的两种产OTA青霉,它们更倾向于侵染富含高蛋白和高NaCl的食物,如奶酪和咸肉,后者也是储藏谷物中OTA的主要产生者[43]。

以食品中的发生率和产OTA能力为依据,将A. westerdijkiae、A. steynii、A. niger、A. welwitschiae、A. carbonarius、P. nordicum和P. verrucosum列为导致食品中发生OTA污染的主要真菌。因此,是检测、预防和控制OTA的关键目标[3]。但事实上,并不是所有菌株都可以一如既往地产生OTA,环境因素的改变对以上真菌的生长、产毒能力及产毒量的多少均具有不同程度的影响,同一菌株的不同分离株中同样存在产OTA和非产OTA菌株。因此,以往的研究中可能存在误判。目前分离、鉴定的产OTA菌株仍在增加,深入的研究和更精确的数据对于更好地表征真菌群中其他可能的产OTA真菌是非常必要的。

2 OTA的产生机制

2.1 OTA生物合成基因

真菌中合成次级代谢产物的基因通常在染色体上成簇存在[44]。2005年,首次克隆并鉴定了存在于OTA生物合成基因簇中的编码基因聚酮合酶基因(polyketide synthase,PKS)和非核糖体肽酶基因(nonribosomal peptide synthetase,NRPS),它们是OTA生物合成基因簇中的核心基因,分别作为次生代谢产物参与聚酮合肽的生物合成[45-46]。OTA是聚酮化合物衍生物,其结构中由聚酮组成的异香豆素部分被认为是由PKS催化的。之后在NRPS催化下,异香豆素部分通过羧基与L-苯丙氨酸连接构成OTA整体结构[47]。从基因水平上发现pks和nrps基因在A. ochraceus、A. westerdijkiae、A. carbonarius和P. verrucosum的OTA生物合成中起关键作用,nrps基因缺失可导致A. carbonarius OTA生物合成的失败[15, 48-51]。此外,OTA生物合成相关基因以及全局调控因子还包括单加氧酶基因(cytochrome P450 monooxygenase,P450)、卤化酶基因(halogenase,HAL)、氯化物过氧化物酶基因、酯酶基因、环化酶基因(cyclase,CYC)、碱性亮氨酸拉链结构调控因子(bZIP)、锌指结构辅助调控因子(Zn2Cys6)等,以上这些基因或调控因子由OTA生物合成相关基因簇编码,唯一的例外是编码酯酶的基因[10, 17, 29, 52]。

通过对曲霉属OTA产毒菌进行详细的比较基因组分析,发现了一个从未描述过的新基因——环化酶otaY基因。该基因位于OTA合成基因簇中otaA和otaB基因之间,编码一种与SnoaLs结构域高度相似的预测蛋白。其可能在OTA生物合成途径初始步骤中的聚酮环化反应中发挥作用[17]。bZIP转录因子otaR1被认为是曲霉属和青霉属物种中结构基因表达的特异性调节因子,已在OTA基因启动子区发现了bZIP结合回文位点[16, 26-27, 53]。到目前为止,这种保守的遗传同源性在A. westerdijkiae、A. steynii、A. niger、A. welwitschiae、A. carbonarius和P. nordicum中均被报道[27, 54]。

对有利于P. nordicum产生OTA条件下的差异表达基因进行分析发现,这些差异表达的基因中含有PKS、NRPS和HAL等参与OTA生物合成的基因[55-56]。之后研究在P. nordicum中鉴定得到一个负责OTA生物合成的假定基因簇,在该基因簇中,有一个开放阅读框编码与卤化酶/氯化物过氧化物酶(参与OTA生物合成途径的酶)同源的假定OTA生物合成蛋白,进而负责OTA的生物合成[55-57]。研究表明,PKS和NRPS的氨基酸序列与所预测的A. niger CBS513.88的OTA基因簇编码序列有较高的相似性[58]。不同曲霉属和青霉属真菌中OTA生物合成相关基因也大致相同,且位于同一基因簇中,但在遗传学上存在种内差异,如A. niger CBS513.88的基因组编码OTA簇,而A. niger ATCC 1015和ATCC 9029则缺失OTA簇[59]。此外,PKS编码核心簇外的基因已在一些物种中被报道,这些基因可参与OTA合成,并在特定条件下可能与聚类PKS编码基因的表达产生互补[16]。

随着真菌基因组测序和遗传操作技术的发展,调控OTA生物合成的关键基因不断显现。但相较于黄曲霉毒素B1、伏马菌素、脱氧雪腐镰刀菌烯醇等被广泛研究的真菌毒素来说,OTA合成相关调控网络及遗传背景尚不十分清楚。对目前所发现的OTA产毒菌基因组的比较分析支持了OTA生物合成一致途径的存在,但OTA的系统、完善生物合成途径还需进一步验证。

2.2 OTA生物合成途径推测

近年来, 科研人员就OTA生物合成进行了大量的研究。截至目前, 已提出了几种OTA的生物合成途径,但关于OTA生物合成如何发生仍存在争议。多数研究表明OTA的生物合成主要从乙酰辅酶A和丙二酰辅酶A开始,而蜂蜜曲菌素、OTα、OTβ、OTB、OTC则是可能中间产物;整个生物合成步骤将通过不同的酶进行催化,包括PKS、NRPS、P450、HAL、氯化物过氧化物酶(包括OTβ的氯原子)以及最新发现的SnoaL环化酶(记为otaY),而酯酶是催化途径中的最后一步[11-16, 47]。一些研究中描述了次生代谢产物蜂蜜曲菌素似乎在OTA生物合成中不起作用 [14, 49, 60],而保护苯丙氨酸羧基的OTC酯也在Huff和Hamilton[13]的研究中被发现没有作为中间体的作用。同样,Gallo等[15]也不认为OTC参与OTA生物合成(由于在A. carbonarius液体培养中未检出)。目前,OTA合成途径以及中间产物的研究还只是猜测,有些可能不完全正确。

关于OTA生物合成途径的最新研究表明,PKS(OtaA)可能是潜在的OTA合成启动酶,OtaA催化乙酰辅酶A和丙二酰辅酶A形成7-甲基蜂蜜曲菌素[12],而otaY可能参与了环化作用[17]。然后被P450(otaC)催化氧化生成OTβ,NRPS催化OTβ与L-β-苯基丙氨酸生成OTB,最后,OTB被HAL(otaD)氯化成OTA[12],该途径对后续OTA生物合成研究具有重要意义(图1[12])。随着科学技术的发展,以往对OTA生物合成途径的推测在不断被推翻或更正,可以确定的是,在科研人员的不断努力下真实的OTA生物合成途径终将浮出水面。

3 OTA的控制策略

3.1 防控方法

避免农作物收获前感染是防控真菌毒素污染的关键一环,在农业生产中防控OTA污染的最好办法是遵从标准的农业规范开展种植,据报道,良好的农业规范可降低葡萄酒中80%的OTA[61]。此外,作物育种技术,如培育出抗OTA污染新品种,将在对抗真菌侵染的源头发挥关键作用。

目前,生物、物理、化学防治技术在农业生产中广泛应用,可在生产的不同阶段(生长期、采收期和加工/储存期)选择适合的OTA防控手段(图2)。生物防治作为一种可持续的OTA防治手段已引起了人们极大的兴趣[3]。多种不产毒真菌具有对抗产毒真菌的潜力,可通过降低OTA产毒菌菌群密度来减轻农作物中OTA的污染[62]。Beauveria bassiana(球囊白僵菌)就是其中之一,使用其处理葡萄园,可使不同季节的OTA污染减少80%以上,因此,它可作为一种有效的“生物杀菌剂”[63]。哈茨木霉(Trichoderma harzianum)是一种寄生型真菌,能主动附着在竞争真菌上并对其菌丝进行酶解,特别是与某些杀菌剂进行比较后发现,T. harzianum在不同条件下对不同测试真菌物种的抑制均具有可比性,包括OTA的产毒菌A. carbonarius [64]。

化学杀菌剂是目前农业生产中常用的真菌防控手段,如嘧菌环胺、抑菌灵、霉双酚、嘧菌酯、敌螨普、赛德福、抑霉唑、多菌灵和咪鲜胺等商用杀菌剂均能有效减少真菌的定植和OTA的合成[3, 65-67]。电解氧化水(electrolyzed-oxidizing water,EOW)可作为农业化学品的有效替代品,如Magistà等[68]发现EOW能有效控制葡萄上的A. carbonarius和OTA的污染。研究人员还发现部分植物的精油也可以起到干扰真菌毒素合成的作用,复合精油(肉桂醛、柠檬醛、丁香酚和薄荷醇)可以成功用于控制贮藏玉米中真菌的生长和霉菌毒素的产生[69-70]。

另外,温度、水分、光照和气体等物理调控手段也能抑制真菌生长和毒素合成。众所周知,较低的温度和水分往往更有利于采后水果和食物的储存。研究发现,完全干燥的谷物,在水分活度低于0.7aw和低于20 ℃环境下的储存时间更长[71]。而4 ℃储存可以完全抑制果蔬中产毒真菌生长和OTA的合成,但在该过程中还应关注低温对水果品质的影响[72]。一般来说,未包装的产品储存温度为 5～10 ℃,包装的产品应为15～20 ℃,水分活度应低于0.75～0.8[73]。此外,气体可作为保护剂在真菌防控中发挥作用,降低食品中的分子氧含量或提高二氧化碳分压,可有效减少食品品质的劣变,抑制微生物的增殖[74]。Zhang等[75]的研究结果表明,UV-B对A. ochraceus和A. carbonarius的生长均有极强的抑制作用,两种真菌在UV-B辐射下的致病性均显著降低。因此,光是有效防治真菌毒素污染的潜在绿色防控策略。

3.2 脱毒方法

3.2.1 物理脱毒方法

为避免粮食和食品的浪费以及因损耗造成的损失,可对受OTA污染的谷物、食品进行脱毒处理。在物理脱毒技术中,伽马(γ)射线辐照和紫外线(UV)等光也可用于去除谷物和食品中的OTA。国内外学者基于γ射线辐照法进行了全面的研究,他们发现γ射线辐照处理不仅能抑制黄曲霉A. flavus和赭曲霉A. ochraceus的生长,还可显著降低污染粮食中OTA的浓度[76-77]。其中10 kGy的辐照剂量对玉米中OTA的降解率为50%[77],而20 kGy的辐照剂量对玉米中OTA的降解率可达61.1%[76]。在γ射线对不同基质中OTA降解情况的研究中发现,水溶液中的OTA较食品基质中的OTA对γ射线辐射更敏感,8.6 kGy可将溶解在水中的OTA完全降解,但30.5 kGy的辐照剂量仅可降解食品基质中 10%～25%的OTA[77-78]。联合臭氧和电子束辐照降解OTA效果显著,响应面优化实验结果表明,12 kGy 的电子束辐照以及50 mg/L的臭氧处理 30 s 对OTA降解效果最佳[79]。为了实际应用,科研人员研究了较短波长UV-B对10 μg/mL OTA标准溶液的降解率,实际降解效率在15 d内可达到96.50%[75]。

使用吸附材料去除OTA的方法经济环保且易于操作,除传统吸附材料活性炭、膨润土外,壳聚糖(天然多糖)的使用可大大提高对OTA及其他霉菌毒素的吸附效率[80]。Zhao等[81]合成了一种交联壳聚糖-戊二醇复合物,其OTA吸附率可达97%,且不受孵育条件限制,如添加剂量、接触时间及pH值。壳聚糖所展现的较强吸附能力主要因其主链上存在氨基和羧基,因此对真菌毒素和环境污染因子表现出很高的吸附能力[5, 80]。高温烘烤也是脱除OTA的方法之一,但受加工食品种类及可能产生的毒性降解产物限制,导致该方法存在争议。在对调味后开心果热加工的研究中发现,烘烤(120、150 ℃,50 min) 和微波辐射加热(6、10 min)可有效降低自然和人工侵染样品中60%以上的真菌毒素,包括OTA和多种黄曲霉毒素(aflatoxins, AFs),并且不会对开心果的味道和外观造成影响。

此外,冷等离子体被认为是一种具备灭活各种致病性和腐败微生物,以及净化食品中真菌毒素功能的新技术,其在预防或减少食物加工过程中OTA污染方面具有巨大潜力[82]。目前已报道了冷等离子体对多种受真菌毒素污染坚果和谷物具有脱毒作用。经冷等离子体处理的受OTA污染咖啡的毒性被降低到“微毒性”,其他研究团队也在冷等离子体处理受污染椰枣果实[83]和大麦[84]的研究中观察到了类似的现象,且不会影响加工产品的营养和感官特性。研究表明,该新技术可成为食品和粮食加工过程中减少真菌发生和降解毒素的替代方法。

3.2.2 生物脱毒方法

生物脱毒法是目前被发现的最环保高效的真菌毒素降解方法,表现出最高的特异性和环境友好性。生物法是指使用某些酶或微生物来对受OTA污染的食品和粮食进行脱毒处理,将其转化为毒性较低的化合物或发挥吸附作用。目前已发现许多微生物,如乳酸菌、酵母菌、芽孢杆菌、某些细菌和丝状真菌等能够降解OTA,它们去除OTA的作用模式包括:通过细菌细胞壁吸附与OTA分子结合和通过细菌产生的活性代谢物或酶进行生物降解[5, 85-86]。部分微生物,如乳酸杆菌已被广泛用于食品中的真菌毒素净化工作[5, 85-86]。此外,乳酸菌、酵母菌、芽孢杆菌等也被报道具备吸附OTA的能力。Shukla等[87]从韩国泡菜中分离出一株枯草芽孢杆菌,将其固定在食用海藻酸盐复合材料中用于减少红酒中的OTA,他们发现该材料可在1 h内吸附红酒中78.5%的OTA,游离和固定化枯草芽孢杆菌之间的OTA吸附能力没有明显差异。

一般的OTA生物降解途径包括OTA分子中酰胺键的水解,并裂解成苯丙氨酸和OTα[86]。可用于OTA降解的微生物酶包括融合水解酶和羧肽酶(ZHPCP)、醇脱氢酶(ADH3)、羧肽酶(carboxypeptidase,CP)、酰胺酶等 [88-89]。最近的一项研究从Stenotrophomonas acidaminiphila中鉴定出一种超高效酶ADH3,该酶可通过充当酰胺水解酶而将OTA转化为无毒OTα[90]。而N-酰基-L-氨基酸酰胺水解酶Na可作为ADH3的同工酶,增强ADH3稳定性,提高Stenotrophomonas sp. CW117对OTA的降解效果,这是首次关于同工酶提高另一种高效解毒酶在体内稳定性的研究[91]。Azam等[92]将玉米赤霉烯酮水解酶(ZHD)和羧肽酶(CP)的单个基因结合构建了一种重组融合酶(ZHDCP),该酶能够在30 min内(pH=7,温度30 ℃下)将OTA完全降解,而CP也可发挥同样的作用。OTα途径被认为是OTA转化中最有效的途径之一。此外,Peng等[93]从Brevundimonas naejangsanensis ML17菌株的代谢物中纯化了4种新型OTA降解酶,即BnOTase1、BnOTase2、BnOTase3和BnOTase4。这4种酶均能将OTA水解成OTα,且对HEK293细胞没有明显的细胞毒性,表明这些酶减轻了OTA的毒性。先前在A. niger中鉴定出一种具有降解OTA功能的未知金属酶,其在37 ℃和pH=7.5的条件下,可降解99.8%的OTA(25 h内)[94]。这种金属酶水解OTA的酰胺键,产生OTα和苯丙氨酸。随后,Zhao等[95]从A. niger W-35菌株中筛选出一种具有OTA降解能力的酶,并将其鉴定为赭曲霉毒素酶(OTase)。目前OTase在大肠杆菌BL21中成功表达,12 h内OTA降解率高达85.1%[95]。因此,新型OTA降解酶不断被挖掘,该领域的研究在OTA防治工作的推进过程中具有重要意义。

3.2.3 化学脱毒方法

臭氧处理作为一种安全、环保、低成本和易于操作的脱毒手段,已在降解OTA及其他真菌毒素方面广泛研究[96]。在臭氧处理对玉米赤霉烯酮(ZEN)和OTA以及玉米品质影响的研究中发现,臭氧能有效降解玉米中的OTA含量(100 mg/L臭氧处理 180 min 可使玉米中的OTA显著降低70.7%),但臭氧处理后玉米水分含量降低,玉米的白度(增加)和黄度(减少)分别随时间的增加而有所改变,玉米脂肪酸值显著升高,玉米品质略有变化[97]。同样,臭氧处理也是去除葡萄干中OTA和真菌污染的有效方法。使用该方法可降解葡萄干中60%以上的OTA,且未导致酚类物质浓度的显著降低[98]。臭氧所具有的强氧化作用可能对食品中的酚类化合物、有机酸等营养因子造成不利影响[5]。因此,选择合适的处理条件是高效利用臭氧脱毒的关键。

许多酸、碱、氧化剂等化学试剂被验证具备脱除或降解OTA的作用。最近的一项研究发现乳酸、柠檬酸和乙酸等有机酸在减少葡萄渣中的OTA方面比盐酸更有效[83]。而Na2S2O4可用于减少黑胡椒中的真菌毒素(OTA和AFs),而不损害黑胡椒的外观及品质。当前,从食品安全的角度考虑,化学脱毒方法的确定和使用需要严格遵守相关法律法规的要求,在不断的探索过程中,已有许多毒性和危害性较大的化合物被禁止用于食品加工行业。开发和研究新型安全环保型化学脱毒制剂是现阶段必须关注的研究课题。

4 结论与展望

在自然界中,OTA作为一种天然污染物广泛存在于霉变食品和饲料中,已知90多种植物和动物来源的食物都存在OTA暴露的风险,对人类和动物的健康构成潜在威胁[35, 99]。目前,OTA产毒菌全基因组数据库的不断丰富,使得产毒菌的种属鉴定更加精准,也将更有利于对OTA生物合成途径、合成基因簇及相关基因的探索。随着科学技术的发展,以往对OTA生物合成途径的推测以及菌种分类问题在不断被推翻或更正,可以确定的是,在科研工作者的不断努力下OTA相关领域的奥秘也终将揭晓。

OTA产毒菌分布范围广泛,OTA毒素污染可以发生在“从农田到餐桌”的每个环节。因此,针对OTA等真菌毒素的控制需要重视“全链条控制”和“源头防控”,并且“重在防菌”,尽量阻断毒素的产生甚至阻断菌的侵染。基于以上防控思路,OTA毒素及其产毒菌的防控工作应在农作物种植阶段就被重视,在此之后的收获、储存、运输和加工环节也是防控产毒真菌侵染及毒素产生的关键时段[3]。此外,保障食物安全须重视损耗问题,对已经受真菌毒素污染的农产品原料可进行脱毒处理,实现毒素污染原料的安全利用。与传统物理、化学防控手段相比,生物防治和生物脱毒技术具有特异性强、环境友好、无污染无残留、条件温和、持久性强、可持续性好等优点,具有十分广阔的市场前景;但目前也存在活性不高、见效慢、广谱性差、稳定性差等弱点,亟须广大科研工作者深入探究和攻关。

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Production Mechanisms and Control Strategies of Ochratoxin A in Food

XING Fuguo, LIU Yibing, WANG Gang

(Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing 100193, China)

Abstract：Ochratoxin A (OTA) is a toxic secondary metabolite mainly produced by fungi from the genera Aspergillus and Penicillium, and it has nephrotoxicity, hepatotoxicity, teratogenicity, neurotoxicity, potential carcinogenicity, and is one of the mycotoxins of great concern worldwide. However, the classification of OTA-producing fungi, OTA biosynthetic pathway and regulatory mechanism are still controversial, which restricts the efficient and accurate control of OTA contamination in food. Therefore, the main OTA-producing fungi in Aspergillus and Penicillium were systematically sorted out and classified. In particular, some strains of A. ochraceus once considered as the main toxigenic fungi were re-identified as A. westerdijkiae based on genomic comparison data, and the toxigenic ability of the main OTA-producing fungi was introduced. The OTA biosynthetic gene clusters, key biosynthetic and regulatory genes were systematically sorted out and introduced, especially the new gene, the cyclase otaY gene, which may be involved in catalyzing the polyketide cyclizing reaction in the initial step of OTA biosynthesis. Based on the latest research results, the OTA biosynthetic pathway was further improved. According to the different stages of food production, the biological, physical and chemical control and detoxification strategies of OTA-producing fungi were sorted out. The biocontrol methods against OTA-producing fungi, and the biodegradation bacteria and detoxification enzymes for OTA were introduced, and the advantages and disadvantages of different methods were compared and discussed. Finally, it was proposed that the control of OTA contamination in food should be based on the idea of “whole chain control” and “source prevention and control” to ensure food safety and people’s life and health. The advantages and disadvantages of biological control and biological detoxification technology were discussed. It was pointed out that a green and safe biological control strategy had broad application prospects and was the key direction of future research.

Keywords：ochratoxin A; regulatory gene; biosynthetic pathway; prevention and control; biodegradation

中图分类号：TS201.3

文献标志码：A

doi：10.12301/spxb202300325

文章编号：2095-6002(2023)04-0026-12

引用格式：邢福国,刘一冰,王刚. 食品中赭曲霉毒素A的产生机制及污染防控策略[J]. 食品科学技术学报,2023,41(4):26-37.

XING Fuguo, LIU Yibing, WANG Gang. Production mechanisms and control strategies of ochratoxin A in food[J]. Journal of Food Science and Technology, 2023,41(4):26-37.

收稿日期：2023-05-24

基金项目：国家重点研发计划课题(2022YFD2100104);广东省自然科学基金资助项目(2022A1515010037)。

Foundation: National Key Research and Development Program of China (2022YFD2100104);Guangdong Province Natural Science Foundation of China (2022A1515010037).

第一作者：邢福国,男,研究员,博士,主要从事农产品真菌毒素防控理论与技术方面的研究。

(责任编辑：李 宁)