微生物学报  2022, Vol. 62 Issue (5): 1600-1612   DOI: 10.13343/j.cnki.wsxb.20210580.
http://dx.doi.org/10.13343/j.cnki.wsxb.20210580
中国科学院微生物研究所，中国微生物学会

文章信息

张娅, 曹成亮, 李荣鹏, 蒋继宏. 2022
ZHANG Ya, CAO Chengliang, LI Rongpeng, JIANG Jihong.
糖丝菌属放线菌研究进展
Recent advance on the genus Saccharothrix
微生物学报, 62(5): 1600-1612
Acta Microbiologica Sinica, 62(5): 1600-1612

文章历史

收稿日期：2021-09-28
修回日期：2022-01-09
网络出版日期：2022-01-29
 Abstract              PDF               Figures               Tables
引用本文
张娅, 曹成亮, 李荣鹏, 蒋继宏. 糖丝菌属放线菌研究进展[J]. 微生物学报, 2022, 62(5): 1600-1612.
Zhang Ya, Cao Chengliang, Li Rongpeng, Jiang Jihong. Recent advance on the genus Saccharothrix[J]. Acta Microbiologica Sinica, 2022, 62(5): 1600-1612.
糖丝菌属放线菌研究进展
张娅 , 曹成亮 , 李荣鹏 , 蒋继宏     
江苏师范大学生命科学学院, 江苏省药用植物生物技术重点实验室, 江苏 徐州 221116
收稿日期：2021-09-28；修回日期：2022-01-09；网络出版日期：2022-01-29
基金项目：国家自然科学基金(31770613)；江苏省研究生科研与实践创新计划(KYCX21_2609)；徐州市科技计划(KC20049)
摘要：1984年美国著名放线菌分类学家Labeda建立的糖丝菌属(Saccharothrix)，是典型的丝状稀有放线菌重要类群之一。糖丝菌的气生菌丝在孢子形成过程中通常呈现锯齿状形态，细胞壁含meso-二氨基庚二酸，磷酸类脂主要包括磷脂酰乙醇胺，优势甲基萘醌是MK-9(H4)和MK-10(H4)，基因组中16S rRNA基因的特异性诊断核苷酸序列为CAC(607–609)和GTG(617–619)。近年来基因组学研究证实，糖丝菌基因组中存在丰富的聚酮合成酶、非核糖体多肽合成酶等基因簇，具有生物合成化学结构新颖、生物活性多样的次生代谢物与酶产物的潜能，且研究证实糖丝菌能够代谢产生已知抗生素的衍生物或新骨架结构的抗生素，如二硫吡咯酮类、内酰胺类、蒽环类和氯霉素等新抗生素，在抗病毒、抑菌和抗肿瘤等方面具有巨大的医药价值。同时，糖丝菌也是工业酶制剂生产菌种资源的新成员，在酶制剂应用方面具有较强的开发潜力，其代谢产生的几丁质酶、纤维素酶等新型活性酶在现代农业以及轻工业等领域有着广泛应用。另外，糖丝菌凭借自身独特的遗传代谢多样性在土壤有机污染物降解和重金属污染修复中扮演着重要角色。结合近期本实验室发表的一株糖丝菌新种，查阅相关文献资料，本文从糖丝菌属的分类学典型特征、基因组学、次级代谢产物生物合成以及产酶应用开发进行了综述，以期为进一步挖掘糖丝菌的应用潜力提供理论基础。
关键词：糖丝菌属    基因组挖掘    次级代谢产物    酶活性    
Recent advance on the genus Saccharothrix
ZHANG Ya , CAO Chengliang , LI Rongpeng , JIANG Jihong     
Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Sciences, Jiangsu Normal University, Xuzhou 221116, Jiangsu, China
Received: 28 September 2021; Revised: 9 January 2022; Published online: 29 January 2022
*Corresponding author: CAO Chengliang, Tel/Fax: +86-516-83403515; E-mail: chengliangcao@jsnu.edu.cn.
Foundation item: Supported by the National Natural Science Foundation of China (31770613), by the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX21_2609) and by the Science and Technology Plan Project of Xuzhou City (KC20049)
Abstract: The genus Saccharothrix was established in 1984 by Labeda, a famous American taxonomist of actinobacteria. This genus is an important group of rare actinomycetes with filamentous hyphae, and most species have zigzag aerial hyphae during sporulation. They contained meso-diaminopimelic acid in cell wall, abundant phosphatidylethanolamine in phospholipids, MK-9(H4) and MK-10(H4) as the principal menaquinones, and the genus-specific motifs CAC (607–609) and GTG (617–619) in the 16S rRNA gene. Recent studies of genome mining have confirmed the existence of non-ribosomal peptide synthetase genes with high frequency in the genomes of Saccharothrix spp., which have the potential to produce structurally-novel secondary metabolites and enzyme products with diverse activities. Further, Saccharothrix can produce derivatives of known antibiotics or antibiotics with new structures, such as dithiopyrrolones, lactams, anthracyclines, and chloramphenicol, which have a great value in antiviral, antibacterial and antitumor treatment. Moreover, Saccharothrix serves as a new microbial resource for the production of industrial enzyme preparations, which has strong development potential in the application of enzyme preparations. New active enzymes such as chitinase and cellulase generated by the metabolism of Saccharothrix are widely used in modern agriculture, light industry and other fields. Owing to the unique genetic and metabolic diversity, Saccharothrix plays a key role in the degradation of organic pollutants and remediation of heavy metal pollution in soil. On the basis a novel species of Saccharothrix discovered by our laboratory and relevant literature, we reviewed the typical taxonomic characteristics, genomics, secondary metabolites, and enzyme development of Saccharothrix, aiming to provide a scientific basis for further mining the Saccharothrix strains with application potential.
Keywords: Saccharothrix    genome mining    secondary metabolites    enzymatic activity    

糖丝菌属(Saccharothrix)隶属于放线菌门(Actinobacteria)，放线菌纲(Actinobacteria)，假诺卡氏菌目(Pseudonocardiales)，假诺卡氏菌科(Pseudonocardiaceae)。目前该属共有21个有效描述种和3个亚种，该属模式种是分离自澳大利亚土壤的Saccharothrix australiensis[1]。基于不依赖纯培养的宏基因组学[2]、宏转录组学、宏蛋白质组学和DNA稳定同位素探针(DNA-SIP)[3]等现代前沿技术，研究发现糖丝菌广泛分布在土壤、植物组织或根际中，甚至在诸如沙漠、盐碱地、洞穴、金属矿床以及湖泊或海洋沉积物等极端环境中也有糖丝菌的踪迹。

糖丝菌是典型的丝状稀有放线菌，能够产生多种新型生物活性代谢物，对人类肿瘤细胞、植物病原性和产毒素真菌以及包括耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus)在内的多种耐药病原体及病毒具有抑制活性[4]，是新型抗生素的重要来源。此外，一些糖丝菌还能产生几丁质酶、纤维素酶等活性酶用来治疗各种真菌类感染疾病、降解纤维素和有机污染物等，在生物医药、现代农业和环境治理等方面有着广泛的应用潜力。近年来基因组学技术突飞猛进，研究表明糖丝菌基因组中含有丰富的与次生代谢产物相关的功能基因簇，新骨架、新功能活性代谢产物通过基因簇克隆、改造，以及菌株共培养等方法而被发现[5]，为新药研发、农业发展和环境污染治理提供了新的解决方案。

1 糖丝菌属系统分类 1.1 糖丝菌属典型特征

1984年，Labeda等首次从土壤中分离出一株能产生新型氨基糖苷类抗生素的菌株，结合其形态特征和系统发育特性，以S. australiensis为模式种建立放线菌新属——糖丝菌属[6]。随后分别经过Labeda等[7]和Zhi等[8]两次修正，将邻近菌属的放线菌陆续重新分类纳入到糖丝菌属中，包括来自拟诺卡氏菌属的Nocardiopsis coeruleofusca和Nocardiopsis mutabilis、马杜拉放线菌属的Actinomadura longispora以及指孢囊菌属的Dactylosporangium variisporea等[9]。相反，根据16S rRNA特征核苷酸分析结果，一些糖丝菌被重新归属到邻近属，如Lechevalieria aerocolonigenes、Lentzea albidocapillata、Lentzea flava、Lentzea violacea、Lentzea waywayandensis、Crossiella cryophilis、Goodfellowia coeruleoviolacea、Umezawaea tangerinus[10–11]。当然，也有近年来加入糖丝菌属的新成员，如2020年本课题组从新疆荒漠中分离出的S. deserti[12]、2017年Bouznada等从撒哈拉沙漠分离出的S. ghardaiensis[13]等。

糖丝菌的营养菌丝(直径约0.5–0.7 μm)和气生菌丝通常断裂成球形或杆状，无运动。营养菌丝呈黄色至棕黄色，少数菌株呈现其他颜色，如S. deserti和S. tamanrassetensis在ISP 2培养基上为深红棕色，气生菌丝在孢子形成过程中通常呈“之”字形，部分菌株产生黄色至棕色的可溶性色素[12, 14]。糖丝菌为革兰氏阳性，需氧，对溶菌酶敏感，过氧化氢酶阳性，生长温度为10–45 ℃，其中S. mutabilis耐80 ℃高温[15]。除S. carnea[16]和S. espanaensis[7]等部分菌株外，大部分糖丝菌能水解明胶，利用酪蛋白和淀粉。细胞壁含meso-二氨基庚二酸，无甘氨酸。全细胞水解物以半乳糖、鼠李糖和甘露糖为特征性糖。磷脂模式为PII型或PIV型，包含磷脂酰乙醇胺(phosphatidylethanolamine，PE)、羟基磷脂酰乙醇胺(hydroxy-phosphatidylethanolamine，OH-PE)，S. australiensis和S. stipae[17]的磷脂为典型的PII型。MK-9(H4)和MK-10(H4)是主要的甲基萘醌。脂肪酸主要含有iso-C16:0，C17:1ω8c，iso-C15:0。无分枝菌酸。DNA的(G+C)含量为67.0–76.0 mol%，16S rRNA基因特异性诊断核苷酸序列为CAC (607–609)和GTG (617–619)，糖丝菌属及其近缘菌属分类学特征见表 1。

表 1. 糖丝菌属及其近缘菌属的分类学特征 Table 1. Taxonomy characteristics of the genus Saccharothrix and closely related genera
Characteristics Saccharothrix[6] Lentzea[18] Lechevalieria[11] Actinosynnema[19] Umezawaea[20]
Cell Cocci/
rod-shaped		 Rod-shaped Cocci/
rod-shaped		 Rod-shaped Cocci/
rod-shaped
pH 6.0–9.0 5.0–11.0 5.0–11.0 6.0–8.5 6.0–8.0
T/℃ 10–45 10–37 28–30 28–30 20–30
NaCl tolerance (%, W/V) 0–3 0–4 0–4 0–2 0–4
Polar lipidsd PE, OH-PE, PI,
PIM, DPG, PG		 PE, DPG, PG, PI PE PE, OH-PE,
PI, PIM, DPG		 PE
Whole-cell sugar Gal, Rha, Man Gal, Man, Rib Gal, Rha, Man Gal, Man Gal, Rha
Major cellular
fatty acids		 iso-C16:0
C17:1ω8c
iso-C15:0		 iso-C14:0
iso-C15:0
iso-C16:0
anteiso-C15:0		 iso-C16:0
anteiso-C15:0
C16:1ω7c
anteiso-C17:0		 C17:0
anteiso-C17:0
iso-C16:0		 iso-C14:0
iso-C15:0
iso-C16:0
iso-C16:1
DNA G+C content (mol%) 67.0–76.0 68.6–79.6 68.0–71.4 71.0–73.0 74.0
Gal: galactose; Man: mannose; Rib: ribose; Rha: rhamnose. PE: phosphatidylethanolamine; PG: phosphatidylglycerol; PI: phosphatidylinositol; DPG: diphosphatidylglycerol; PIM: phosphatidylinositolmannoside; OH-PE: hydroxy-phosphatidylethanolamine.
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基于16S rRNA基因序列的系统发育进化分析(图 1)，糖丝菌属21株有效发表种聚集为一个大分支，其中本实验室报道的新物种S. deserti BMP8144T与S. lopnurensis YIM LPA2hT的16S rRNA基因序列相似性达到98.9%，位于一个亚分支内[12]。此外，糖丝菌属与梅泽宾夫氏菌属(Umezawaea)的进化距离最近，其次是束丝放线菌属(Actinosynnema)、涅什瓦列属(Lechevalieria)、伦茨菌属(Lentzea)和放线动孢菌属(Actinokineospora)[19–20]聚类在一起，亲缘关系密切。

图 1 基于16S rRNA基因序列邻近法构建的糖丝菌属有效发表种的系统发育树 Figure 1 Neighbor-joining phylogenetic tree based on 16S rRNA gene sequences of the validly published species of the Saccharothrix. Numbers at nodes indicate levels of bootstrap support based on a neighbor-joining analysis of 1 000 resampled datasets, only values > 50% were given. Bar, 5 substitutions per 1 000 nucleotide positions.
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1.2 基因组及基因资源发掘

放线菌产生的许多抗生素都是通过非核糖体多肽合成酶(nonribosomal peptide synthetases，NRPSs)或聚酮合酶(polyketide synthases，PKSs)的途径进行生物合成的[21]。糖丝菌基因组中NRPSs基因的高频率存在是其产生大量生物活性次级代谢产物的有力证据[22]。截至2021年9月，GenBank、JGI和GTDB的数据库中共收录了17株糖丝菌的基因组序列，基于Type Strain Genome Server (https://tygs.dsmz.de/)服务器的系统发育分析如图 2。antiSMASH (V5.2.0)基因组注释预测显示糖丝菌属菌株的NRPSs和PKSs基因簇相当丰富(表 2)，推测糖丝菌产生的次生代谢产物与酶在治疗细菌、真菌和病毒类感染疾病，抗肿瘤和抗结核等方面有重要作用。如最近Feng等报道了S. texasensis 6-C的完整基因组大小为9.04 Mb，有9个NRPSs、5个I型PKSs基因簇，能编码大量抗菌活性物质，该基因组信息有助于阐明S. texasensis 6-C生物防治马铃薯晚疫病的分子机制[23]；本实验室通过多相分类获得的S. deserti BMP B8144T基因组大小为10.80 Mb，其中1 213个基因包含43个与次级代谢产物相关的推定基因簇，包括14个NRPSs、9个I型PKSs、2个II型PKSs，推测该菌株产生的次生代谢产物具有广泛的生物活性，如抗肿瘤、抗结核等[12]。

图 2 基于TYGS服务器中糖丝菌基因组序列的系统发育树 Figure 2 Phylogenomic tree based on genome sequences of the genus Saccharothrix in the TYGS server. Tree inferred with FastME 2.1.6.1 from GBDP distances calculated from genome sequences. The branch lengths are scaled in terms of GBDP distance formula d5. The numbers above branches are GBDP pseudo-bootstrap support values > 60% from 100 replications, with an average branch support of 94.6%. Bar, 2 nucleotide substitution per 100 nucleotides.
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表 2. 糖丝菌属基因组特征 Table 2. Features of Saccharothrix genomes
Species Genome size/bp CDSs rRNAs tRNAs BGCs PKS NRPS
S. algeriensis DSM 44581T 6 878 582 6 066 12 49 29 5 5
S. australiensis DSM 43800T 7 861 373 6 694 12 52 33 10 8
S. carnea CGMCC 4.7097T 8 918 169 7 939 7 59 38 11 10
S. coeruleofusca DSM 43679T 7 721 092 7 222 15 57 24 8 8
S. deserti BMP B8144T 10 832 261 9 959 5 71 49 19 14
S. ecbatanensis DSM 45486T 9 689 237 8 599 12 58 39 9 13
S. espanaensis DSM 44229T 9 360 653 8 436 12 56 33 6 11
S. longispora DSM 43749T 8 375 440 7 529 12 57 29 9 10
S. saharensis DSM 45456T 8 924 967 7 995 12 52 34 8 9
S. syringae NRRL B-16468T 10 929 570 9 301 12 53 48 16 14
S. tamanrassetensis CECT 8640T 8 053 586 7 177 6 50 33 6 10
S. texasensis DSM 44231T 9 178 199 8 137 12 52 36 10 9
S variisporea DSM 43911T 9 408 895 8 387 12 53 29 10 10
S. violaceirubra DSM 45084T 7 354 386 6 781 12 52 31 7 10
Saccharothrix sp. ALI-22-I 10 300 059 9 372 3 59 41 13 16
Saccharothrix sp. CB00851 9 304 003 8 377 4 53 43 11 15
Saccharothrix sp. NRRL B-16314 8 934 493 8 023 9 58 41 14 9
Saccharothrix sp. NRRL B-16348 10 896 489 9 728 20 67 43 15 10
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随着后基因组时代的到来，挖掘发现新型活性天然产物已成为近年来国内外研究的热点，实验证明挖掘放线菌基因组是寻求新天然化合物的有效途径。从海量的基因序列中筛选鉴定出有价值的基因簇，是基因组挖掘(genome mining)的关键步骤。如Lin等筛选鉴定了Saccharothrix sp. ST-888中与磷霉素有关的生物合成基因簇，为阐明天然磷酸盐的生物合成机制奠定了基础[24]。由于实验条件及自然因素等制约，放线菌基因组中与活性代谢产物相关的基因簇常处于低表达量或沉默状态[25]，激活放线菌次级代谢产物合成基因簇的表达具有十分重要的意义。如Gorniaková等通过遗传操作激活S. espanaensis DSM 44229的一个隐秘生物合成基因簇，获得了新型手霉素(manumycins)[5]。通过放线菌的培养条件优化或在培养过程中添加诱导物以及与其他微生物联合培养等手段都有可能激活放线菌基因簇的成功表达，如Bakour等发现优化S. tamanrassetensis DSM 45947的碳氮源可促进产生新型抗生素[26]。

2 糖丝菌属应用潜力研究 2.1 次生代谢产物研究

抗生素在临床上的广泛使用使得许多病原菌和病毒耐药能力增强，因此继续寻找结构新颖、高效低毒的新型抗生素成为当下天然活性产物研究的热点。研究表明，糖丝菌能够产生已知抗生素的衍生物或新骨架结构的抗生素，如二硫吡咯酮类、内酰胺类、蒽环类和氯霉素[27–28]等抑菌或抗癌类抗生素(表 3)。2013年Wang等从S. xinjiangensis NRRL B-24321中分离获得两种新的16元大环内酯类聚酮化合物tianchimycin A和B[29]，2020年Babadi等也从同种不同菌株Act24Zk中分离纯化出化合物saccharopyrone，对人宫颈癌HeLa细胞KB3.1具有较好的细胞毒性，IC50值达到5.4 µmol/L[30]。

表 3. 糖丝菌产生的天然活性产物 Table 3. Natural active products of Saccharothrix strains
Species Compounds Biological activities
S. algeriensis[31] Dithiolopyrrolone antibiotics Broad-spectrum antibacterial
S. australiensis DSM 43800[6] Antibiotic LL-BM-782-E Antibacterial
S. espanaensis[5, 32] Saccharothrixins (A, B, C)
Saccharomicins (A, B)
Manumycins
Antibiotic LL-C19004-D		 Antibacterial
Antitumor and immunosuppressive
Farnesyltransferase inhibitor
Antibacterial
S. mutabilis[7] Capreomycin
Polynitoxin		 Antibacterial
Antibacterial
S. syringae NRRL B‑16468[33] Nocamycin Antibacterial and antitumor
S. xinjiangensis[29–30] Caerulomycin M
Accharopyrone
Saccharonoic acid
Tianchimycin (A, B)
Swalpamycin B		 Antitumor
Antitumor
Antitumor
Antibacterial
Antibacterial
Saccharothrix sp. ABH26[34] Cyanogrisides (I, J)
Caerulomycins (A, B, C, D, E, F)		 Antibacterial
Antifungal, antiparasitic and antitumor
Saccharothrix sp. A1506[35] Saccharothriolide (A, B, C, D, E, F, C2) Antibacterial, antifungal and antitumor
Saccharothrix sp. MI-293-N4[36] Kinamycins 1 and 2
Saccharothrixones (D, E, F, G, H, I)		 Antibacterial
Anticancer and antibacterial
Saccharothrix sp. DSM12931[37] Pluraflavins Antitumor
Saccharothrix sp. 10-10[38] Saccharothrixone D
Tetracenomycin X		 Antibacterial
Antitumor
Saccharothrix sp. PAL54[28] Chloramphenicol Antibacterial
Saccharothrix sp. AJ9571[39] Ammocidin (A, B, C, D) Apoptosis inducer
Saccharothrix sp. SA 103[40] Mutactimycin PR Antibacterial
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近年来，国内研究者对于S. syringae NRRL B-16468代谢产物的研究相对较深。诺卡霉素是特特拉姆酸家族的天然产物，具广泛的抗菌活性及抗肿瘤作用，确切抑菌作用还未证实，但与之紧密相关的化合物tirandamycin和streptolydigin已被证实是细菌RNA聚合酶(ribonucleic acid polymerase，RNAP)的抑制剂[41]，因此诺卡霉素可能是RNAP的抑制剂。随着高通量技术的快速发展，基因组挖掘方法不断精进，诺卡霉素的生物合成途径也不断被完善。2017年Mo等鉴定出诺卡霉素合成相关基因簇并提出假定生物合成途径：诺卡霉素骨架由5种Ⅰ型聚酮合酶(NcmA I，NcmA II，NcmA III，NcmA IV，NcmA V)和一种非核糖体多肽合成酶(NcmB)组成，一种环化酶(NcmC)催化，5种酶(NcmEDGOP)剪裁以及5种酶(NcmNJKIM)起调节作用[33]。随后证实，NcmP是一种甲基转移酶[42]，短链脱氢酶NcmD与一种未知酶负责诺卡霉素F的C-10氧化[43]，但由于诺卡霉素生物合成路线长，诺卡霉素F之前的合成步骤还未完全明确(图 3)，仍需继续深入研究。

图 3 诺卡霉素的假定生物合成途径[33, 41–42] Figure 3 The putative biosynthetic pathway of nokamycin[33, 41–42].
图选项

2.2 产酶应用研究

放线菌一直以来都是工业生产酶制剂的重要来源。国内学者研究发现S. yanglingensis Hhs.015能产生一种新型几丁质酶[44]，具有广阔的应用前景。在生态农业领域，几丁质酶能降解害虫和植物病原真菌的不同结构，作为应用开发潜力巨大的生防微生物菌剂，近年受到广泛关注。在医药领域，几丁质酶是抗真菌药物设计研究的理想靶酶，可用来治疗各种真菌类感染疾病。另一个重要的医学应用是几丁质酶可催化几丁质和壳聚糖反应生成无毒、较好生物相容性的衍生物，这些衍生物往往具有抗菌、抗肿瘤和调节人体免疫等生理活性[45]。

糖丝菌能产生内切β-1, 4-葡聚糖酶，该酶是纤维素酶系中研究最为广泛深入的一种酶，随机水解β-1, 4-葡聚糖苷键，将长链的纤维素截断，从而形成纤维低聚糖，被广泛应用于纺织、啤酒、饲料和造纸等领域[46]。由S. australiensis IFO 14444，S. texasensis NRRL B-16134，S. coeruleofusca ATCC 35108，S. mutabilis ATCC 23892，S. syringae DSM 43886，S. longispora ATCC 31109等数种优选糖丝菌产生的内切葡聚糖酶制剂可应用于洗涤剂或织物柔软组合物中，或在纺织工业中用于改善纤维素或织物的特性[47]。S. mutabilis NM-6-5能在高温下分解纤维素，在工、农业废弃物处理中具有较高的应用价值[48]，具体代谢途径和功能机制值得进一步研究。

2.3 污染修复研究

值得一提的是，在有机物污染降解和重金属污染修复方面糖丝菌也有不俗的表现。Saccharothrix sp. PYX-6以蒽、菲、芘为唯一碳源，能降解含4个苯环的稠环芳烃化合物芘，中间代谢产物是邻苯二甲酸[49]，这与以前报道的Mycobacterium sp. PYR-1的降解途径不同。Saccharothrix sp. BG以邻苯二甲酸二(2-乙基己基)酯为唯一碳源，在48 h内可将其浓度从20 mg/L降解到2 mg/L，在污水处理系统中能发挥较好的作用[50]。Saccharothrix sp. APL5能降解聚琥珀酸丁二烯(polybutadiene-styrene)[51]。糖丝菌也是生物修复重金属污染过程中的重要参与者。从韩国[52]、德国[53]、伊朗[54]的不同重金属污染土壤中分离出的S. violacea LM 036、S. albidocapillata DSM 44073、S. waywayandensis Tosca4、Saccharothrix sp. UTMC 2163和Saccharothrix sp. UTMC 2185显示出对镉、镍等重金属有良好的耐受性，可修复重金属污染土壤，可能的修复机制是通过产生酶和次级代谢产物以及生物吸附作用抵抗重金属胁迫。但由于微生物降解有机物、抵抗重金属反应机制复杂，具体降解途径并未完全研究清楚，有待继续深入。

3 展望

生活在如沙漠、海洋沉积物等极端环境中的糖丝菌类群表现出多样化的生理遗传性和独特的代谢特征，具有丰富的次级代谢产物基因簇，产生的活性产物表现出了新颖的化学结构和高效低毒的特性。诚然，自然环境中的糖丝菌远不止目前的21个有效描述种，新物种资源的挖掘任重道远。注重加强极端环境中的糖丝菌类群的研究，尤其是难培养的菌株，要尝试从纯培养技术上有所突破，在技术优化和创新方面下足功夫，如基于膜扩散的培养方法、微流控培养方法和基于细胞分选的培养方法[55]。同时，随着各种高通量组学技术的快速发展，使用高通量测序分析和靶向方法分离培养新型微生物是研究糖丝菌的重要手段之一。利用反向基因组学对未经培养的微生物进行定向分离和靶向培养，有可能解决尚未培养微生物生命树分支中物种的分离、培养和表征问题[56]。或者采用非靶向培养方法：通过高通量技术深度测序，结合文献确定培养基等条件进行大规模培养分离纯化，对最终纯化的菌株进行菌种鉴定，从基因水平上再次确认菌株的分类学属性[57]。

研究证实，一些稀有放线菌的代谢产物表现出特异的酶抑制剂活性，能够阻断病毒的复制途径，在临床上对病毒引起的疾病起到一定治疗作用。邻近糖丝菌属的Lentzea chajnantorensis H45T代谢合成的二烯和单烯糖苷化合物lentzeaosides A–F对人体免疫缺陷病毒Ⅰ型(human immunodeficiency virus type Ⅰ)整合酶显示出不同水平的抑制活性，并已应用于临床治疗[58]。早在1991年学者就发现S. mutabilis R869-90代谢合成的化合物fluvirucin对A型流感病毒株具有抑制活性[59]，这提示糖丝菌在抗病毒药物研发道路上也有潜在的应用前景。正值当下，新型冠状病毒肺炎(corona virus disease 2019)在全世界范围内肆虐横行，迅速变异的病毒株的传染性和致死率不断提高，而临床仍缺乏效果明显的靶向治疗药物，这一严峻形势向天然活性化合物的药物研发提出了新的挑战。

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