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Engineering interventions for enhanced sophorolipid biosynthesis: from native producers to recombinant platforms. 工程干预增强皂荚脂生物合成:从本地生产者重组平台。
IF 4.2 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-13 DOI: 10.1007/s11274-025-04733-9
Yashika Raheja, Saurabh Singh, Rakhi Kapoor, Amit Kumar Chaurasia, Ajay Kumar, Vivek Kumar Gaur

Sophorolipid (SL) are glycolipid biosurfactants with growing industrial relevance as sustainable alternatives to petrochemical surfactants. This review highlights the advances in SL genetics and pathway architecture, transcriptional and process level regulation, and comparative performance of native producers versus recombinant platforms. It emphasizes the transition from empirical optimization to rational, systems guided strategies integrating advance metabolic engineering strategies including pathway optimization to divert carbon flux toward the SL module, balance redox/energy demands with growth, and tailor congener profiles. We further evaluated the current industrial feasibility, technology used by several companies highlighting progress increasing titers and productivities alongside persistent constraints in production, reliance on costly feedstocks, different fermentation methods, process parameters, and challenging downstream recovery. Key research gaps include incomplete understanding of regulatory control, limited systematic flux redistribution, and insufficient techno-economic integration. We outline future priorities for CRISPR enabled and omics guided rewiring, secretion and tolerance engineering, deployment of low cost/waste substrates, and standardized, scalable purification. These directions define a roadmap to robust, cost competitive SL manufacturing and clarify where recombinant hosts can complement or extend capabilities beyond Starmerella bombicola.

Sophorolipid (SL)是一种糖脂类生物表面活性剂,作为石化表面活性剂的可持续替代品,具有日益增长的工业意义。本文综述了SL遗传学和途径结构、转录和过程水平调控以及本地生产者与重组平台的比较性能方面的进展。它强调从经验优化到理性的转变,系统引导的策略整合了先进的代谢工程策略,包括途径优化,将碳通量转向SL模块,平衡氧化还原/能量需求与生长,以及定制同类剖面。我们进一步评估了目前的工业可行性,几家公司使用的技术,强调了在生产持续限制、依赖昂贵的原料、不同的发酵方法、工艺参数和具有挑战性的下游回收的情况下,提高滴度和生产率的进展。主要的研究空白包括对监管控制的不完全理解、有限的系统性流量再分配以及技术经济一体化不足。我们概述了CRISPR支持和组学指导下的重组、分泌和耐受性工程、低成本/废弃底物的部署以及标准化、可扩展的纯化的未来重点。这些方向定义了一个强大的、具有成本竞争力的SL制造路线图,并阐明了重组宿主可以补充或扩展Starmerella bombicola之外的能力。
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引用次数: 0
Strengthening physiological resilience, osmotic adjustment, and ion homeostasis in water-deficit stressed muskmelon via ACC deaminase-producing rhizobacterial partnership. 通过ACC脱氨酶产生的根细菌伙伴关系增强缺水胁迫甜瓜的生理弹性、渗透调节和离子稳态。
IF 4.2 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-13 DOI: 10.1007/s11274-025-04750-8
Mohammad Altaf, Mohammad Shahid, Talat Ilyas, Shiv Charan Kumar, Shareen Niyazi

Here, ACC deaminase ACC Deaminase producing rhizobacteria, Priestia aryabhattai MD-85 (Accession no. PV155249.1) and Enterobacter cloacae MD-79 (Accession no. PV155250.1), were assessed for their potential to enhance water-deficit stress tolerance in muskmelon. Both strains produced ACC Deaminase and exhibited drought tolerance, with MD-79 showing 78.9 ± 7.6 µM α-ketobutyrate mg⁻¹ protein h⁻¹ at 18%-PEG, and MD-85 showing 68.4 ± 5.4 µM α-ketobutyrate mg⁻¹ protein h⁻¹ at 21%-PEG. Both strains produced multi-functional growth-promoting substances under PEG-induced stress, conferring their significant drought tolerance potential. Increasing water stress negatively impacted growth and physiological characteristics of soil-grown muskmelon plants. However, ACC Deaminase-producing strains, especially when applied in combination (P. aryabhattai MD-85 + E. cloacae MD-79), effectively mitigated adverse effects of drought stress. For instance, under 3%-polyethylene glycol (PEG)-induced stress in muskmelon, co-inoculation (MD-79 + MD-85) enhanced root length (44.3%), shoot length (47.6%), root dry and fresh wight ratio (40.7%), leaf dry and fresh wight ratios (51.7%), total chlorophyll (41.5%), and carotenoids (38.8%). Further, bacterial consortia significantly (p ≤ 0.05) enhanced chlorophyll colour index (56.7%), net photosynthetic rate (64.3%), Fv/Fm (50.8%), stomatal conductance (64.3%) and relative water content (62.3%) in leaf tissues of 3%-PEG-stressed muskmelon. Single/combined bacterial inoculation lowered drought-induced oxidative stress markers in muskmelon. Moreover, bacterial partners strengthened antioxidant enzymes in water-deficit affected muskmelon. The 15%-PEG + MD-79 + MD-85 treatment exhibited greater increase in catalase (79.3%), ascorbate peroxidase (65.3%), peroxidase (55.7%), and superoxide dismutase (72%), activities over their respective untreated controls. Additionally, bacterial strains modulated ion homeostasis in PEG-stressed muskmelon roots, enhancing drought tolerance. Notably, combined inoculation synergistically enhanced drought tolerance compared to single-strain treatments. This study emphasizes the potential of ACC Deaminase-producing PGPR as a sustainable and long-term strategy to improve muskmelon resilience under water-deficit condition by modulating physiological, biochemical, and ionic responses. These findings underscore the use of PGPR in drought management to enhance crop productivity and stress tolerance.

这里,ACC脱氨酶产生ACC脱氨酶的根细菌,Priestia aryabhattai MD-85。PV155249.1)和阴沟肠杆菌MD-79(文献登记号:PV155250.1)对甜瓜抗水分亏缺胁迫的潜力进行了评估。这两种菌株都产生ACC脱氨酶并表现出耐旱能力,其中MD-79在18%-PEG下显示78.9±7.6 μ M α-酮丁酸mg - h -毒血症,MD-85在21%-PEG下显示68.4±5.4 μ M α-酮丁酸mg - h -毒血症。两个品系在peg诱导的胁迫下均产生了多功能促生长物质,具有显著的抗旱潜力。增加水分胁迫对土栽甜瓜植株的生长和生理特性有负面影响。然而,ACC脱氨酶产生菌株,特别是当组合使用时(P. aryabhattai MD-85 + E。泄殖腔MD-79),有效减轻干旱胁迫的不利影响。例如,在3%-聚乙二醇(PEG)诱导的胁迫下,共接种(MD-79 + MD-85)使甜瓜根长(44.3%)、茎长(47.6%)、根干鲜比(40.7%)、叶干鲜比(51.7%)、总叶绿素(41.5%)和类胡萝卜素(38.8%)增加。此外,细菌联合体显著(p≤0.05)提高了3%- peg胁迫甜瓜叶片叶绿素颜色指数(56.7%)、净光合速率(64.3%)、Fv/Fm(50.8%)、气孔导度(64.3%)和相对含水量(62.3%)。单/联合细菌接种降低了甜瓜干旱诱导的氧化应激标记物。此外,细菌伴侣增强了缺水甜瓜体内的抗氧化酶。15%-PEG + MD-79 + MD-85处理的过氧化氢酶(79.3%)、抗坏血酸过氧化物酶(65.3%)、过氧化物酶(55.7%)和超氧化物歧化酶(72%)活性比各自未处理的对照显著增加。此外,细菌菌株调节peg胁迫下甜瓜根系的离子稳态,增强耐旱性。值得注意的是,与单株处理相比,联合接种可协同提高抗旱性。本研究强调了ACC脱氨酶产生PGPR作为一种可持续和长期的策略,通过调节生理、生化和离子反应来提高甜瓜在缺水条件下的抗逆性。这些发现强调了PGPR在干旱管理中的应用,以提高作物生产力和抗逆性。
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引用次数: 0
Ecological and functional dynamics of gut microbiota in the model insect, silkworm Bombyx mori. 模式昆虫家蚕肠道微生物群的生态学和功能动力学。
IF 4.2 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-13 DOI: 10.1007/s11274-026-04784-6
Abrar Muhammad, Chao Sun, Yongqi Shao

The silkworm (Bombyx mori) has emerged as a powerful invertebrate model for gut microbiome research due to its simple yet representative gut microbiota, cost-effective rearing, and established germ-free systems. This review synthesizes current knowledge on the ecological drivers and functional roles of silkworm gut microbiota, emphasizing its interaction with host health, environmental adaptation, and biotechnological applications. The microbial community of silkworms is highly plastic, shaped by various intrinsic (developmental stage, sex) and extrinsic (diet, environmental conditions) factors. Key microbial taxa, including Enterococcus, Bacillus, Acinetobacter, Pseudomonas, and Staphylococcus, form a dynamic core community with demonstrated probiotic attributes. These microbes contribute to nutrient metabolism (such as cellulose digestion and amino acid synthesis), immune modulation (through the production of antimicrobial peptides), and detoxification (by degrading xenobiotics). Meanwhile, their dysbiosis correlates with reduced growth, silk yield, and pathogen resistance. Notably, several gut symbionts produce or stimulate natural antimicrobial proteins, including bacteriocins (such as enterococcin LX) and host-derived antimicrobial peptides, which exhibit activity against microbial pathogens. Understanding these microbial associations is crucial for developing microbe-based probiotic formulations, antimicrobial therapies, and enzyme-driven bioprocesses to enhance sericultural productivity and sustainability. Despite progress, significant gaps remain in our understanding of host-microbe coevolution, immune-microbiota crosstalk, and the genetic basis of microbial resilience. Future research integrating multi-omics approaches and gnotobiotic models will unravel mechanistic insights, enabling targeted manipulation of the silkworm microbiota for agricultural, environmental, and medical innovations.

家蚕(Bombyx mori)由于其简单而具有代表性的肠道微生物群,具有成本效益的饲养和已建立的无菌系统,已成为肠道微生物组研究的强大无脊椎动物模型。本文综述了家蚕肠道菌群的生态驱动和功能作用,重点介绍了其与宿主健康、环境适应和生物技术应用的相互作用。家蚕的微生物群落具有高度的可塑性,受到各种内在因素(发育阶段、性别)和外在因素(饮食、环境条件)的影响。关键微生物类群,包括肠球菌、芽孢杆菌、不动杆菌、假单胞菌和葡萄球菌,形成了一个具有益生菌特性的动态核心群落。这些微生物有助于营养代谢(如纤维素消化和氨基酸合成)、免疫调节(通过产生抗菌肽)和解毒(通过降解异种生物)。同时,它们的生态失调与生长、产丝和抗病性降低有关。值得注意的是,一些肠道共生体产生或刺激天然抗菌蛋白,包括细菌素(如肠球菌素LX)和宿主来源的抗菌肽,它们对微生物病原体具有活性。了解这些微生物关联对于开发基于微生物的益生菌配方、抗菌疗法和酶驱动的生物工艺以提高蚕桑生产力和可持续性至关重要。尽管取得了进展,但我们对宿主-微生物共同进化、免疫-微生物群串扰和微生物恢复力的遗传基础的理解仍存在重大差距。整合多组学方法和生物模型的未来研究将揭示机制见解,使有针对性地操纵桑蚕微生物群用于农业、环境和医学创新。
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引用次数: 0
Flower-shaped ZnO nanoparticles from Lactococcus lactis LAB2: potential selective anti-cancer activity via oxidative stress modulation. 乳球菌LAB2中的花状ZnO纳米颗粒:通过氧化应激调节的潜在选择性抗癌活性
IF 4.2 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-13 DOI: 10.1007/s11274-025-04691-2
Ameneh Tatari, Fatemeh Salimi, Safiyeh Aghazadeh, Saba Amini

Biosynthesized zinc oxide nanoparticles (ZnO-NP2) produced using Lactococcus lactis culture supernatant demonstrate exceptional selectivity as anticancer agents. These flower-like nanoparticles maintained 96.44% viability in normal HUVEC cells, while reducing the viability of HCT116 and K562 cancer cells to 58.92% and 39.24%, respectively, at a concentration of 0.25 mg/mL. Acridine orange-ethidium bromide staining confirmed dose-dependent apoptosis induction, with K562 cells exhibiting a combined apoptotic and necrotic population of 61.66%. Oxidative stress analysis revealed sophisticated cell-type-specific redox modulation, including a 46.9% upregulation of catalase compared to the control in HCT116 cells, elevated lipid peroxidation, and increased levels of nitric oxide and glutathione. Gene expression analysis revealed dramatic alterations in the apoptotic pathway: HCT116 cells exhibited a 29.68-fold upregulation of BAX, while K562 cells demonstrated a 0.05-fold downregulation of BCL2. Physicochemical characterization confirmed successful synthesis with protein coating (evidenced by FTIR peak at 1635.95 cm⁻¹), negative surface charge (-25 to -30 mV), and crystalline flower-like morphology. Paradoxically, ZnO-NP2 showed antioxidant activity in cell-free DPPH assays (63.15% reduction) despite pro-oxidant effects in cancer cells. ZnO-NP2 induced selective cancer cell apoptosis through modulation of oxidative stress and activation of the intrinsic apoptotic pathway in vitro, suggesting preliminary potential for development as targeted anticancer agents, pending comprehensive in vivo validation and mechanistic studies.

利用乳酸乳球菌培养上清制备的生物合成氧化锌纳米颗粒(ZnO-NP2)作为抗癌剂具有特殊的选择性。这些花状纳米颗粒在正常HUVEC细胞中维持96.44%的活力,而在浓度为0.25 mg/mL时,HCT116和K562癌细胞的活力分别降低至58.92%和39.24%。吖啶橙-溴化乙啶染色证实了剂量依赖性的凋亡诱导,K562细胞出现61.66%的凋亡和坏死。氧化应激分析揭示了复杂的细胞类型特异性氧化还原调节,包括与对照相比,HCT116细胞中过氧化氢酶上调46.9%,脂质过氧化水平升高,一氧化氮和谷胱甘肽水平升高。基因表达分析显示凋亡通路发生显著变化:HCT116细胞BAX上调29.68倍,而K562细胞BCL2下调0.05倍。物理化学表征证实成功合成了蛋白质涂层(FTIR峰在1635.95 cm - 1),负表面电荷(-25至-30 mV)和结晶花状形态。矛盾的是,ZnO-NP2在无细胞DPPH实验中显示出抗氧化活性(降低63.15%),尽管在癌细胞中具有促氧化作用。在体外实验中,ZnO-NP2通过调节氧化应激和激活内在凋亡途径诱导选择性癌细胞凋亡,提示其作为靶向抗癌药物的初步潜力,有待于全面的体内验证和机制研究。
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引用次数: 0
Recent advances in metabolic engineering for microbial production of L-tyrosine. 微生物生产l -酪氨酸的代谢工程研究进展。
IF 4.2 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-13 DOI: 10.1007/s11274-025-04776-y
Kaixin Shi, Yahong Shi, Anying Ji

L-Tyrosine, an important aromatic amino acid, has broad applications in food, feed, pharmaceuticals, nutraceuticals, and materials industries, with consistently growing market demand. Conventional production methods face drawbacks such as low efficiency and significant environmental impact. In contrast, microbial cell factories offer a promising alternative due to their environmental friendliness, sustainability, and controllability. This review systematically summarizes recent advances in metabolic engineering strategies for L-tyrosine production, including key enzyme overexpression and engineering, pathway optimization, and enhancement of precursor, cofactor, and transport systems. It also explores prospective research directions to address ongoing challenges such as complex metabolic networks and product inhibition, including systems biology-guided global optimization, dynamic regulation, and diversified substrate utilization. Overall, this review aims to provide a theoretical and technical foundation for advancing efficient, economical, and sustainable L-tyrosine biomanufacturing.

l -酪氨酸是一种重要的芳香氨基酸,在食品、饲料、医药、营养保健品、材料等行业有着广泛的应用,市场需求不断增长。传统的生产方法存在效率低、环境影响大等缺点。相比之下,微生物细胞工厂因其环境友好、可持续性和可控性而提供了一个有前途的选择。本文系统地综述了l -酪氨酸生产的代谢工程策略的最新进展,包括关键酶的过表达和工程、途径优化、前体、辅因子和运输系统的增强。它还探讨了未来的研究方向,以解决当前的挑战,如复杂的代谢网络和产物抑制,包括系统生物学指导的全局优化,动态调节和多样化的底物利用。本文旨在为推进高效、经济、可持续的l -酪氨酸生物制造提供理论和技术基础。
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引用次数: 0
Recent advances in microbial production of odd-chain fatty acids. 奇链脂肪酸微生物生产的最新进展。
IF 4.2 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-13 DOI: 10.1007/s11274-025-04769-x
Rudolphus Antonius Timmers, Marta de Vicente, Aurora Rosa-Masegosa, Elvira Romero, Elia Tomás-Pejó, Cristina González-Fernández

The production of odd-chain fatty acids (OCFAs) is gaining increasing importance due to their diverse applications in food, chemical, and biofuel industries. These fatty acids, which are relatively rare in nature, can be produced from renewable carbon sources through microbial fermentation processes. This review covers the significance of OCFAs in the market and their occurrence, followed by a detailed exploration of their production in mixed and single strain cultures. Specifically, the anaerobic fermentation (AF) conditions and feedstocks used to produce short OCFAs (SOCFAs), such as propionic, valeric, and heptanoic acids are discussed. Additionally, the production of long OCFAs (LOCFAs) by single strains is focusing on yeast, bacteria, and microalgae. Novel approaches for LOCFAs generation from waste carbon sources are also reviewed. This work delves both into the manipulation of microbial communities covering bioaugmentation and process optimization for bioenrichment in open mixed cultures and genetic manipulation in single-strain systems. Finally, the potential for scalable and sustainable production of OCFAs through microbial processes is discussed, as well as the technological advances needed to optimize these pathways.

由于奇链脂肪酸在食品、化学和生物燃料工业中的广泛应用,其生产越来越受到重视。这些脂肪酸在自然界中相对罕见,可以通过微生物发酵过程从可再生碳源中生产。本文综述了ocfa在市场上的意义及其发生情况,然后详细探讨了它们在混合和单菌种培养中的生产情况。具体来说,厌氧发酵(AF)条件和用于生产短OCFAs (SOCFAs)的原料,如丙酸,戊酸和庚酸进行了讨论。此外,单菌株生产长OCFAs (LOCFAs)的重点是酵母、细菌和微藻。本文还综述了利用废弃碳源生成LOCFAs的新方法。这项工作深入研究了微生物群落的操作,包括开放混合培养中生物富集的生物增强和工艺优化,以及单菌株系统中的遗传操作。最后,讨论了通过微生物过程可扩展和可持续生产OCFAs的潜力,以及优化这些途径所需的技术进步。
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引用次数: 0
Microbial exopolysaccharide pullulan-based seed priming combined with Chlorella vulgaris enhances salinity tolerance in maize. 微生物胞外多糖普鲁兰与普通小球藻联合催种提高玉米耐盐性。
IF 4.2 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-08 DOI: 10.1007/s11274-025-04774-0
Camila Vilca Pascuali, Daniela Delgado Pineda, Gilberto Colina Andrade, Ruly Terán Hilares

Salinity is a major abiotic stress limiting global maize (Zea mays L.) production. This study evaluated the biostimulant potential of pullulan, an exopolysaccharide produced by Aureobasidium pullulans ATCC 42,023, applied alone or in combination with the microalga Chlorella vulgaris, to enhance seed sprouting and initial growth under saline environments. Pullulan was biosynthesized in a 5-L bioreactor using glucose as the carbon source, achieving a concentration of 19.23 g/L (0.25 g/g sugar of yield) at an initial glucose level of 100 g/L. Seed priming with pullulan concentrations (2.5-5.0 g/L) significantly promoted coleoptile and root elongation, whereas higher levels (10 g/L) inhibited growth. Notably, the combined application of 5 g/L of pullulan + 20 mg of C. vulgaris alleviated salinity stress (EC: 3.63 dS/m) by reducing oxidative damage, sustaining root activity, and improving plant height and chlorophyll content. Overall, the combined use of pullulan and Chlorella vulgaris enhanced maize performance, highlighting their potential as sustainable seed-priming agents and a promising strategy for managing salt-affected soils in resilient and sustainable agricultural systems.

盐胁迫是限制全球玉米生产的主要非生物胁迫。普鲁兰是一种由小球藻(Chlorella vulgaris)产生的胞外多糖,本研究评估了普鲁兰聚糖单独或与小球藻联合使用在盐水环境下促进种子发芽和初始生长的生物刺激潜力。以葡萄糖为碳源,在5-L生物反应器中合成普鲁兰,在初始葡萄糖水平为100 g/L的条件下,普鲁兰的浓度为19.23 g/L(产糖量为0.25 g/g)。2.5 ~ 5.0 g/L普鲁兰灌种显著促进了胚芽组织和根的伸长,而10 g/L普鲁兰灌种抑制了胚芽组织的生长。5 g/L普鲁兰+ 20 mg乌根草配施可通过降低氧化损伤、维持根系活性、提高株高和叶绿素含量来缓解盐胁迫(EC: 3.63 dS/m)。总体而言,普鲁兰和小球藻的联合使用提高了玉米的性能,突出了它们作为可持续种子引种剂的潜力,以及在抗灾和可持续农业系统中管理受盐影响土壤的一种有希望的策略。
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引用次数: 0
A review on novel strategies to combat multidrug resistance in pathogenic bacteria exploiting synergism between essential oil and antibiotics. 利用精油与抗生素协同作用对抗病原菌多药耐药的新策略综述。
IF 4.2 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-08 DOI: 10.1007/s11274-025-04775-z
Ishita Mazumder, Muskan Rehman, Falguni Deshmukh, Shrushti Shah, Akshita Singh, Sudha Ramaiah, Elizabeth Annie George, Anand Anbarasu
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引用次数: 0
Mechanisms of microbial community restructuring and metabolic pathway modulation during biological nitrogen removal in livestock wastewater under combined antibiotic stress. 抗生素联合胁迫下畜禽废水生物脱氮过程中微生物群落重组及代谢途径调控机制
IF 4.2 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-08 DOI: 10.1007/s11274-025-04782-0
Xianjin Qiu, Jian Huang, Hua Zhang, Jinhua Wang, Tao Luo, Chunhua He
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引用次数: 0
Decoding the regulatory role of AmiC in amicoumacins production through transcriptomics and metabolic profiling in Bacillus subtilis fmb60. 通过枯草芽孢杆菌fmb60的转录组学和代谢分析解码AmiC在amicoumacins生产中的调节作用。
IF 4.2 3区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2026-01-07 DOI: 10.1007/s11274-025-04773-1
Antuo Hu, Yangfan Fu, Di Ren, Haifeng Tang, Qingzheng Zhu, Hucheng Jiang, Yanan Liu, Saikun Pan, Jie Yang, Xiaoying Bian

Amicoumacins are a group of NRPS-PKS antibiotics produced by Bacillus species that exhibit broad-spectrum antibacterial, anti-inflammatory, and anticancer activities. Despite their promising pharmacological potential, the regulatory mechanisms underlying their biosynthesis remain largely unexplored, hindering the development of rational approaches for yield enhancement. In this study, we investigated the regulatory function of the amiC gene in the biosynthesis of amicoumacin by Bacillus subtilis fmb60. An amiC-overexpressing strain was constructed and displayed a significant increase in total amicoumacin production, which was correlated with larger inhibition zones against both Staphylococcus aureus and Escherichia coli. Conversely, deletion of amiC led to a substantial decrease in amicoumacin yield, to only 23.5% of the wild-type level (a 4.26-fold reduction). Metabolomic profiling further confirmed that AmiC functions as a positive regulator of multiple amicoumacin derivatives. Transcriptomic analysis of the knockout strain identified 68 differentially expressed genes, with KEGG enrichment indicating significant involvement of flagellar assembly, bacterial chemotaxis, and two-component system pathways. Mechanistic insights further suggested that loss of amiC perturbs cellular metabolism by enhancing chemotaxis and regulatory signaling, thereby diverting metabolic flux away from secondary metabolite biosynthesis. Collectively, these findings demonstrate that amiC act as a key positive regulator of amicoumacin biosynthesis and represents a promising target for metabolic engineering to improve antibiotic production.

Amicoumacins是一组由芽孢杆菌产生的nrpps - pks抗生素,具有广谱抗菌、抗炎和抗癌活性。尽管它们具有良好的药理潜力,但其生物合成的调控机制仍未被充分探索,阻碍了提高产量的合理方法的发展。在本研究中,我们研究了amiC基因在枯草芽孢杆菌fmb60合成阿米库霉素中的调控作用。构建了过表达amic的菌株,其amicoumacin总产量显著增加,对金黄色葡萄球菌和大肠杆菌均有较大的抑制区。相反,缺失amiC导致amicoumacin产量大幅下降,仅为野生型水平的23.5%(减少4.26倍)。代谢组学分析进一步证实了AmiC作为多种amicoumacin衍生物的正调节因子。敲除菌株的转录组学分析鉴定出68个差异表达基因,其中KEGG富集表明鞭毛组装、细菌趋化性和双组分系统途径的显著参与。机制研究进一步表明,amiC的缺失通过增强趋化性和调节信号来扰乱细胞代谢,从而使代谢通量偏离次级代谢物的生物合成。综上所述,这些发现表明,amiC是amicoumacin生物合成的关键正调节因子,代表了代谢工程提高抗生素生产的一个有希望的靶点。
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引用次数: 0
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World journal of microbiology & biotechnology
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