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Synergy evaluation of cefepime/enmetazobactam in combination with novel β-lactam/β-lactamase inhibitor combinations (βL/βLICs) against Klebsiella pneumoniae carrying different blaKPC variants. 头孢吡肟/恩美唑巴坦联合新型β-内酰胺/β-内酰胺酶抑制剂(βL/βLICs)对携带不同blaKPC变异的肺炎克雷伯菌的协同作用评价
IF 2.7 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-02-05 DOI: 10.1038/s41429-026-00900-8
Carlo Tascini, Giulia Zocche, Paolo Gaibani
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引用次数: 0
Streptomyces aurantiaciflavus sp. nov., a novel actinomycete isolated from rhizosphere soil with antifungal activity and plant growth-promoting ability. 金酸链霉菌(Streptomyces auantiaciflavus)是一种从根际土壤中分离出来的具有抗真菌活性和促进植物生长能力的新型放线菌。
IF 2.7 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-02-04 DOI: 10.1038/s41429-026-00897-0
Jiaxin Jin, Xue Zhao, Muxi Zhang, Jiayi Xu, Xingbo Wang, Ran Zhang, Yan Xu, Zhen Song, Jia Song, Wensheng Xiang

A novel actinobacterial strain NEAU-NA10T showing antifungal activity and plant growth-promoting ability was isolated from the rhizosphere soil of strawberry seedlings collected from Ya'an City, Sichuan Province, China (28°51' N, 101°56' E). A polyphasic taxonomic study was used to establish the status of strain NEAU-NA10T. 16S rRNA gene sequence analysis revealed that strain NEAU-NA10T belongs to the genus Streptomyces and shares the highest similarity (99.31%) with Streptomyces canarius CGMCC 4.1581T. Whole-genome comparisons with its reference strains demonstrated that the average nucleotide identity (ANIm) and digital DNA-DNA hybridization (dDDH) values ranged from 86.74 to 87.75% and 27.0 to 30.1%, respectively. The phospholipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, and phosphatidylinositol. The diagnostic sugars in cell hydrolysates were determined to be ribose, and the cell wall contained LL-diaminopimelic acid as the diagnostic diamino acid. The predominant menaquinones were MK-9(H4), MK-9(H6) and MK-9(H8). The predominant cellular fatty acids (>10%) were C16:0, C17:0, C18:0, and anteiso-C18:0. Meanwhile, genomic analysis revealed a genome size of 9,459,621 bp and a DNA G + C content of 71.81%, and indicated that strain NEAU-NA10T has the potential to degrade cellulose and produce amylase. Based on phenotypic, chemotaxonomic, and genotypic studies, strain NEAU-NA10T is considered to be a novel species of the genus Streptomyces, for which the name Streptomyces aurantiaciflavus sp. nov. is proposed, with NEAU-NA10T (=MCCC 1K08700T = JCM 36416T) as the type strain.

从四川省雅安市(28°51' N, 101°56' E)草莓幼苗根际土壤中分离到一株具有抗真菌活性和促生长能力的放线菌NEAU-NA10T。采用多相分类学方法确定了菌株NEAU-NA10T的地位。16S rRNA基因序列分析显示,菌株NEAU-NA10T属于链霉菌属,与canarius链霉菌CGMCC 4.1581T相似度最高(99.31%)。与参比菌株的全基因组比较表明,该菌株的平均核苷酸同源性(ANIm)和数字DNA-DNA杂交(dDDH)值分别为86.74 ~ 87.75%和27.0 ~ 30.1%。磷脂谱包含二磷脂酰甘油、磷脂酰乙醇胺和磷脂酰肌醇。细胞水解物中的诊断糖被确定为核糖,细胞壁含有ll -二氨基戊酸作为诊断二氨基酸。以MK-9(H4)、MK-9(H6)和MK-9(H8)为主。主要的细胞脂肪酸为C16:0、C17:0、C18:0和前体细胞C18:0。基因组分析显示,菌株基因组大小为9,459,621 bp, DNA G + C含量为71.81%,表明菌株NEAU-NA10T具有降解纤维素和产生淀粉酶的潜力。基于表型、化学分类和基因型研究,菌株NEAU-NA10T被认为是链霉菌属的一个新种,并以NEAU-NA10T (=MCCC 1K08700T = JCM 36416T)为型菌株命名为金酸链霉菌(Streptomyces aurantiaciflavus sp. nov.)。
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引用次数: 0
Marinapyrones A and B, new antioxidative α-pyrones produced by soybean rhizosphere-derived actinomycete strain W21-0103. 大豆根际源放线菌W21-0103制备的新型抗氧化α-吡咯酮A和B。
IF 2.7 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-02-04 DOI: 10.1038/s41429-026-00898-z
Satoru Shigeno, Yuki Onishi, Yohei Nishikawa, Takuji Nakashima, Haruko Takeyama, Hiroshi Tomoda, Taichi Ohshiro

Two new α-pyrone compounds designated marinapyrones A (1) and B (2) were isolated along with the known related compound micropyrone B (3) from the culture broth of rhizosphere-derived actinomycete strain W21-0103. The structures of 1 and 2 were elucidated by spectroscopic data analyses, including 1D and 2D NMR. Compounds 1-3 exhibited weak antioxidant activity in a radical scavenging assay.

从根际源放线菌W21-0103培养液中分离到两个新的α-吡酮化合物marinapyrones A(1)和B(2)以及已知的相关化合物micropyrone B(3)。1和2的结构通过波谱数据分析,包括一维和二维核磁共振进行了鉴定。化合物1-3在自由基清除实验中表现出较弱的抗氧化活性。
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引用次数: 0
Biofilm formation and associated biomechanical traits co-segregate with multidrug resistance in typhoidal Salmonella. 伤寒沙门氏菌的生物膜形成和相关的生物力学特性与多药耐药共同分离。
IF 2.7 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-02-03 DOI: 10.1038/s41429-026-00899-y
Mehveen Iqbal, Shaista Urooj, Noor Ul Huda, Fouzia Zeeshan Khan, Zulqarnain Hassan, Anum Khan, Nisar Ahmed Shar, Muhammad Naseem Khan, Anila Siddiqui, Abdul Basit Khan, Saeed Khan, Zulfiqar Ali Mirani

Typhoidal Salmonella continues to pose a severe public health threat, with its management increasingly complicated by the rise of antimicrobial resistance. This study investigated 50 clinical isolates of Salmonella Typhi (S. Typhi) and S. Paratyphi to delineate the association between antibiotic resistance, biofilm formation, and nanoscale mechanical traits. Our results revealed that 22% of isolates were multidrug-resistant (MDR), displaying the classical resistance pattern against ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. Among these resistant isolates, 54% formed biofilms, and this trait was strongly associated with multidrug resistance; 100% of MDR isolates were biofilm-positive (p = 0.001). Atomic force microscopy (AFM) revealed a distinct "hard-shell" bio-mechanical phenotype in biofilm-positive isolates, exhibiting significantly higher stiffness (31.3 ± 9.8 vs. 8.2 ± 2.3 kPa), adhesion force (17.8 ± 4.6 vs. 5.4 ± 1.4 nN), and surface roughness (11.6 ± 3.2 vs. 3.6 ± 1.0 nm) (p < 0.001 for all). This mechanical reinforcement was accompanied by a 2.7-fold increase in cell surface hydrophobicity (80.4 ± 8.9% vs. 30.3 ± 11.9%) and a 13.5-fold enhancement in desiccation survival (40.4 ± 10.7% vs. 3.0 ± 2.9%). Correlation analysis revealed these traits are highly interdependent (ρ = 0.78--0.89, p < 0.001), forming a cohesive "hard-shell" persistence phenotype. In summary, multidrug-resistant Salmonella possesses a unified trait that enhances its structural strength, ability to adhere, and environmental survival.

伤寒沙门氏菌继续构成严重的公共卫生威胁,其管理因抗菌素耐药性的上升而日益复杂化。本研究调查了50株临床分离的伤寒沙门菌(S. Typhi)和副伤寒沙门菌,以描述抗生素耐药性、生物膜形成和纳米尺度力学特性之间的关系。结果显示,22%的分离株具有多重耐药(MDR),表现出对氨苄西林、氯霉素和甲氧苄啶-磺胺甲恶唑的经典耐药模式。在这些耐药菌株中,54%形成生物膜,这一特性与多药耐药密切相关;100%的MDR分离株生物膜阳性(p = 0.001)。原子力显微镜(AFM)显示,生物膜阳性分离株具有明显的“硬壳”生物力学表型,具有明显更高的刚度(31.3±9.8比8.2±2.3 kPa),附着力(17.8±4.6比5.4±1.4 nN)和表面粗糙度(11.6±3.2比3.6±1.0 nm)
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引用次数: 0
Substance Index for Volume 78 第78卷物质索引
IF 2.7 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-27 DOI: 10.1038/s41429-025-00890-z
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引用次数: 0
Author Index for Volume 78 第78卷作者索引
IF 2.7 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-27 DOI: 10.1038/s41429-025-00879-8
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引用次数: 0
Genome mining discovery of aquimarinols, threoninol-containing acylpeptides from Aquimarina muelleri. 基因组挖掘发现水苏氨酸醇类,水苏氨酸类含苏氨酸的酰基肽。
IF 2.7 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-22 DOI: 10.1038/s41429-026-00894-3
Zhihan Zhang, Lihan Zhang

Thioester reductase domain in nonribosomal peptide synthetases catalyzes reductive offloading to produce aldehyde- or alcohol-containing peptides. By genome mining focusing on thioester reductase domains, we isolated aquimarinols A-D, four novel polyketide-peptide hybrid metabolites isolated from the sponge-derived strain Aquimarina muelleri LMG 22569. Structural elucidation of aquimarinols revealed a β-formamidated fatty acid (FA) moiety and a threoninol unit linked by a peptide bond or an ester bond. The biosynthesis of aquimarinols is proposed to proceed via a hybrid trans-AT polyketide synthase-nonribosomal peptide synthetase pathway coupled with modification enzymes.

非核糖体肽合成酶中的硫酯还原酶结构域催化还原卸载产生含醛或含醇肽。通过对硫酯还原酶结构域的基因组挖掘,我们从海绵状菌株Aquimarina muelleri LMG 22569中分离出四种新的聚酮肽杂交代谢物aquimarinols A-D。对海海脂醇的结构分析揭示了一个β-甲酰胺脂肪酸(FA)片段和一个由肽键或酯键连接的苏氨酸醇单元。海海木酚的生物合成是通过反式at聚酮合成酶-非核糖体肽合成酶的杂化途径与修饰酶结合进行的。
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引用次数: 0
Aminoacyl-tRNA-dependent enzymes in natural product biosynthesis: structure-function insights. 天然产物生物合成中的氨基酰基trna依赖酶:结构-功能见解。
IF 2.7 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-22 DOI: 10.1038/s41429-025-00893-w
Yu Zheng, Yanhui Zhao, Shunji Takahashi

Aminoacyl-tRNAs, charged by aminoacyl-tRNA synthetases with cognate amino acids, are essential for protein synthesis in primary metabolism. Beyond this canonical role, increasing evidence highlights their involvement in natural product biosynthesis. In this review, we first describe the biosynthesis of the aminoacyl nucleoside sulfamate ascamycin from Streptomyces sp. 80H647, highlighting the discovery of the alanyl-tRNA synthetase-like enzyme AcmF through an AI-driven "Forecasting Biosynthesis" approach. Leveraging recent advances in AlphaFold 3, we constructed complex models of a broadened repertoire of aminoacyl-tRNA-dependent enzymes to provide preliminary structure-function insights. These include the isoleucyl-tRNA synthetase-like enzyme SbzA, Gcn5-related N-acetyltransferase-fold transferases, cyclodipeptide synthase family enzymes, and lantibiotic dehydratase-like peptide aminoacyl-tRNA ligases. The catalytic mechanisms of these aminoacyl-tRNA-dependent enzymes are summarized in detail in this review.

在初级代谢过程中,氨基酰基trna是蛋白质合成所必需的,由氨基酰基trna合成酶与同源氨基酸结合。除了这个典型的角色,越来越多的证据强调他们参与天然产物的生物合成。在这篇综述中,我们首先描述了从Streptomyces sp. 80H647中提取的氨基酰基核苷磺酸阿斯霉素的生物合成,重点介绍了通过人工智能驱动的“预测生物合成”方法发现的alanyl-tRNA合成酶样酶AcmF。利用AlphaFold 3的最新进展,我们构建了广泛的氨基酰基trna依赖性酶的复杂模型,以提供初步的结构-功能见解。这些酶包括异亮氨酸- trna合成酶样酶SbzA、gcn5相关的n -乙酰转移酶折叠转移酶、环二肽合成酶家族酶和抗生素脱水酶样肽氨基酰基- trna连接酶。本文就这些氨基酰基trna依赖性酶的催化机理作一综述。
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引用次数: 0
Expression of a strain-specific non-ribosomal peptide synthetase from Aspergillus lentulus lead to the discovery of a new fungal alkaloid lentoquinazoline. 从香菇曲霉中表达一种菌株特异性的非核糖体肽合成酶,从而发现了一种新的真菌生物碱——香菇喹唑啉。
IF 2.7 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-22 DOI: 10.1038/s41429-025-00887-8
Shinji Kishimoto, Yuya Masuyama, Kenji Watanabe

Fungi have a potential to produce a variety of natural products for their survival by utilizing dozens of biosynthetic gene clusters (BGCs). Fungal BGCs are typically conserved in species but recent studies showed that many BGCs are maintained in limited number of strains. However, little is reported for the products of strain specific BGCs. In this study, we analyzed publicly available genomic data of human pathogenic fungus Aspergillus lentulus and identified seven strain-specific BGCs in addition to (-)- and (+)-auranthine BGCs. One of these BGCs, leq cluster, was found in nine of thirteen A. lentulus strains and a new compound named lentoquinazoline (1) appeared in the metabolites when non-ribosomal peptide synthetase (NRPS) gene leqA was heterologously expressed in Aspergillus nidulans. The structure of 1 was determined by the combination of 2D NMR analysis and advanced Marfey's method to be composed of anthranilic acid, L-leucine and L-asparagine. Whereas 6-6-6 tricyclic quinazoline-synthesizing NRPSs typically contain an epimerase domain and incorporate one molecule of D-amino acid to the product, LeqA was found to introduce only L-amino acids due to the mutations in the active site of the epimerase domain.

真菌利用数十个生物合成基因簇(BGCs),有可能产生多种天然产物以维持其生存。真菌BGCs通常在物种中保守,但最近的研究表明,许多BGCs维持在有限数量的菌株中。然而,关于菌株特异性bgc产物的报道很少。在这项研究中,我们分析了公开的人类致病真菌香菇曲霉的基因组数据,除了(-)-和(+)-金嘌呤BGCs外,还鉴定了7种菌株特异性BGCs。其中一种bgc为leq簇,在13株香曲霉中的9株中发现,非核糖体肽合成酶(NRPS)基因leqA异源表达时,代谢产物中出现了一种新的化合物,命名为lentoquinazoline(1)。结合二维核磁共振分析和先进的Marfey's方法确定了1的结构由邻氨基苯酸、l -亮氨酸和l -天冬酰胺组成。6-6-6三环喹唑啉合成的NRPSs通常含有一个外旋酶结构域,并在产物中加入一个d -氨基酸分子,而LeqA由于外旋酶结构域活性位点的突变而只引入了l -氨基酸。
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引用次数: 0
Genome mining-based discovery of an atypical fungal non-reducing polyketide synthase encoding dimeric alkylresorcinol biosynthesis. 基于基因组挖掘的非典型真菌非还原聚酮合成酶编码二聚体烷基间苯二酚生物合成的发现。
IF 2.7 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-14 DOI: 10.1038/s41429-025-00891-y
Yuto Homma, Tomoya Hasegawa, Yohei Morishita, Soya Koremura, Akihiro Sugawara, Taro Ozaki, Teigo Asai

Genome mining is a powerful strategy for finding biosynthetic gene clusters (BGCs) for unprecedented natural products and their biosynthetic mechanisms. In this study, to obtain novel type polyketides, we performed genome mining focusing on three perspectives for novelty: 1) amino acid sequence-based classification, 2) unique domain architectures of polyketide synthase, and 3) predicted structural features from protein modeling. As a result, we discovered a BGC consisting of a highly reducing polyketide synthase and a non-reducing polyketide synthase (NR-PKS), which harbors noncanonical tandem acyl carrier protein (ACP) domains and a structurally characteristic thioesterase (TE) domain. Heterologous expression revealed that the cyrl cluster produces a novel dimer of long-chain alkylresorcinolic acid (1). Furthermore, site-directed mutagenesis of each ACP domain revealed that both domains are essential for efficient dimerization. This study provides the first example of a fungal dimer-forming NR-PKS in which the tandem ACP domains work "in-series" with nonredundant roles to construct a dimeric long-chain alkylresorcinolic acid. The in silico analysis suggested that the TE domain led the substrate to a dimerizable form. Since 1 is structurally related to integracins with HIV-1 integrase inhibition, our findings provide insight into integracins biosynthesis and offer a basis for generating new integracin derivatives.

基因组挖掘是为前所未有的天然产物及其生物合成机制寻找生物合成基因簇(BGCs)的有力策略。为了获得新型聚酮,我们从三个方面进行了基因组挖掘:1)基于氨基酸序列的分类;2)聚酮合成酶的独特结构域结构;3)通过蛋白质模型预测结构特征。结果,我们发现了一个由高还原性聚酮合成酶和非还原性聚酮合成酶(NR-PKS)组成的BGC,其中包含非典型串联酰基载体蛋白(ACP)结构域和结构特征硫酯酶(TE)结构域。异源表达表明,环簇产生一种新的长链烷基间苯二甲酸二聚体(1)。此外,每个ACP结构域的定点突变表明,这两个结构域对于有效的二聚化是必不可少的。本研究提供了真菌二聚体形成NR-PKS的第一个例子,其中串联ACP结构域以非冗余的作用“串联”构建二聚体长链烷基间苯二酚酸。硅分析表明,TE结构域导致底物形成二聚化形式。由于1在结构上与整合素与HIV-1整合酶抑制有关,我们的研究结果为整合素的生物合成提供了新的见解,并为生成新的整合素衍生物提供了基础。
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引用次数: 0
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Journal of Antibiotics
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