CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Chenghao Fu,Wenjuan Dai,Aoxiang Liu,Yongxuan Liu,Qingshou Yao,Linghui Kong,Bo Yu,Xiuwen Wang,Jiayang Qin
ε-Poly- l -lysine (ε-PL), typically comprising 25–35 l -lysine residues, is a natural homopolymer with potent antibacterial properties. Its wider use is limited by two key challenges: precise control over peptide chain length and low production yields of low-molecular-weight (low-MW) ε-PL variants. In this study, we addressed these constraints by combining genetic engineering, carbon source modulation, and fermentation optimisation, enabling the targeted production of four well-characterised ε-PL variants. Multiple genetically engineered strains of Streptomyces albulus were developed and evaluated for ε-PL chain distribution. Particularly, S. albulus CICC-Pls880-LysP— co -overexpression of a mutated polylysine synthetase (Pls S880I) and a lysine importer (LysP)—produced ε-PL with chain lengths between 23 and 31 residues when grown in glucose-enriched fermentation broth and between 19 and 30 residues in glycerol-enriched broth. By contrast, the parental strain CICC-Pls-LysP yielded longer polymers (28–34 residues in glucose and 25–32 in glycerol), confirming the effectiveness of enzyme engineering in modulating chain length. Subsequent statistical optimisation of the fermentation medium, coupled with fed-batch cultivation strategies, enabled all four ε-PL variants (28–34, 25–32, 23–31, and 19–30 mer) to achieve production titres exceeding 50 g/L. Notably, supplementing l -lysine during fermentation significantly enhanced the yield of the low-MW variant (23–31 mer), reaching to 75.35 g/L. Antibacterial activity assays revealed a distinct correlation between chain length and efficacy, providing valuable insights into the structure–function relationships of ε-PL. This method, established for selectively synthesising ε-PL variants, overcomes historical yield bottlenecks for low-MW ε-PL, thereby broadening the applications of ε-PL.
研究领域:
生物技术
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微生物发酵
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合成生物学
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高分子科学
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应用微生物学
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2025
·
IF 6.2
Tianbing Zhou,Yuxin Xu,Yingtong Chen,Zhengbin Tang,Erxin Wang,Mengmeng Li,Mingrui Dou,Zhijia Zhang,Tao Zhang,Shujun Huang,Shuxian Gu,Shuai Wang,Ranfeng Sun,Dong Li
Phytophthora capsici causes devastating losses in global pepper production. This study deciphers a sophisticated plant-microbe-metabolite collaboration initiated by rhizosphere-colonizing Streptomyces. We demonstrate that Streptomyces specifically primes pepper root biosynthesis of 6-nitrocoumarin, a nitrated coumarin derivative exhibiting potent broad-spectrum antioomycete activity (EC50: P. capsici 44.39 mg/L, Phytophthora palmivora 47.06 mg/L, Peronophythora litchii 34.92 mg/L). Crucially, this Streptomyces-recruited metabolite functions as a keystone rhizosphere signal, selectively enriching beneficial bacterial consortia while directly disrupting the ABC transporters of pathogens. The restructured microbiome synergistically amplifies plant systemic resistance through upregulating defense genes and enhancing root immunity. Our work establishes 6-nitrocoumarin as a dual-functional inoculant, a direct actinomycete compound and microbiome modulator, revealing a novel plant-microbe codefense paradigm driven by Streptomyces-induced metabolic rewiring for sustainable crop protection.
研究领域:
植物病理学
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微生物生态学
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分子植物-微生物互作
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农业生物技术
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天然产物化学
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作物保护
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根际生物学
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DOI
PubMed
高影响因子
BIOPROCESS AND BIOSYSTEMS ENGINEERING
·
2018
·Vol. 41
·期 5
·729-738
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IF 2.139
Tong Qian-Qian,Zhou Yue-Hui,Chen Xiang-Song,Wu Jin-Yong,Wei Ping,Yuan Li-Xia,Yao Jian-Ming
The production of virginiamycin (VGM) from Streptomyces virginiae was improved by genome shuffling and ribosome engineering companied with a high-throughput screening method integrating deep-well cultivation and the cylinder–plate detecting. First, a novel high-throughput method was developed to rapidly screen large numbers of VGM-producing mutants. Then, the starting population of genome shuffling was obtained through ultraviolet (UV) and microwave mutagenesis, and four mutants with higher productivity of VGM were selected for genome shuffling. Next, the parent protoplasts were inactivated by UV and heat when a fusant probability was about 98%. Streptomycin resistance was used as an evolutionary pressure to extend positive effects on VGM synthesis. Finally, after five rounds of genome shuffling, a genetically stable strain G5-103 was obtained and characterized to be able to yield 251 mg/L VGM, which was 3.1- and 11.6-fold higher than that of the mutant strain UV 1150 and the wild-type strain, respectively.
研究领域:
生物技术
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微生物学
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药学
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DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2022
·Vol. 19
·期 5
·e202200177
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IF 2.745
Susu Lin,Bingbing Ma,Qilin Gao,Jian Yang,Gang Lai,Runhao Lin,Bingxian Yang,Bing-Nan Han,Lian-Hua Xu
Cytochrome P450 enzymes (CYPs or P450s) are ubiquitous heme-dependent enzymes that catalyze the monooxygenation of non-activated C−H bonds to modify the structure of the substrate. In this study, we heterologously expressed CYP107X1 from Streptomyces avermitilis and conducted in vitro substrate screening using the alternative redox partners putidaredoxin and putidaredoxin reductase. CYP107X1 catalyzed the 16α-hydroxylation of progesterone with regio- and stereoselectivity. The spectroscopic analyses showed that CYP107X1 bound progesterone with a relatively high K d value of 65.3±38.9 μM. The K m and k cat values for progesterone were estimated to be 47.7±12.0 μM and 0.30 min −1 , respectively. Furthermore, a crystal structure was obtained of CYP107X1 bound with glycerol from the buffer solution. Interestingly, a conserved threonine was replaced with asparagine in CYP107X1, indicating that it may adopt an unnatural proton transfer process and play a crucial role in its catalytic activity.
研究领域:
生物化学
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酶学
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结构生物学
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DOI
PubMed
高影响因子
Anti-Cancer Agents in Medicinal Chemistry
·
2015
·Vol. 15
·期 3
·285-290
·
IF 2.469
Dongbo Xu,Min Ma,Yongfeng Liu,Ting Zhou,Kexin Wang,Zixin Deng,Kui Hong
PreQ0 base (7-cyano-7-deazaguanine, compound 1) is the biosynthetic precursor of queuosine-tRNA and important synthetic intermediate for bioactive compounds. It was obtained for the first time as a new natural product from a mangrove actinomycete Streptomyces qinglanensis 172205, during the course of searching for anti-cancer compounds from marine microbes. PreQ0 base showed anti-HeLa (IC50 = 62.0 μ g/ml) and anti-HepG2 (IC50 = 80.6 μ g/ml) activities, higher cytotoxicity than the positive control, fluorouracil. Furthermore, it exhibited weak α -glucosidase inhibitory activity, but no obvious antimicrobial and Aβ 1-42 fibrillation inhibitory activities. In silico analysis of the genome of the strain 172205 revealed a putative biosynthetic gene cluster directing the biosynthesis of PreQ0 base. The gene cluster only contained three Open Reading Frames (ORFs), queC, queD and queE. The absence of the key gene queF encoding 7-cyano-7-deazaguanine reductase catalyzing PreQ0 base to PreQ1 base suggested that the strain only has the capacity of accumulation of PreQ0 base as a metabolite, consistent with our observation in chemical identification.
研究领域:
微生物学
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天然产物化学
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海洋生物技术
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癌症药理学
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基因组学
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生物信息学
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DOI
高影响因子
BMC MICROBIOLOGY
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2025
·Vol. 26
·期 1
·77
·
IF 4.2
Zhang Mengfan,Song Zhengxiong,Yang Jinyan,Miao Pu,Wang Hui,Li Haohao,Wang Jun,Kang Yebin
Background This study aimed to determine the optimal fermentation conditions and to characterize extracellular differential metabolites of Streptomyces rochei strain W71. The inhibition rate of its fermentation supernatant against Phytophthora nicotianae was used as the evaluation index to assess anti-oomycete activity. Methods The fermentation conditions of strain W71 were optimized through single-factor experiments combined with response surface methodology (RSM: Plackett–Burman design, steepest ascent, and Box–Behnken design). Untargeted liquid chromatography–mass spectrometry (LC–MS) metabolomic analysis was then performed to identify extracellular metabolites and elucidate the key metabolic pathways involved. Results The optimal fermentation conditions for strain W71 were as follows: maltose: 20.0 g/L, yeast extract powder: 2.5 g/L, NaCl: 1.0 g/L, working volume: 100 mL/250 mL, inoculum size: 5.55%, agitation speed: 200 rpm, initial pH: 8.66, temperature: 29.8 ℃, and fermentation time: 8 days. Under these conditions, the inhibition rate of the fermentation broth reached 92.90%, representing a 6.78-fold increase compared with the pre-optimization level. LC–MS metabolomic analysis identified 1,771 differential metabolites in extracellular extracts after optimization, of which 1,479 were upregulated and 292 were downregulated. The major metabolite classes included organic halogen compounds, organic acids and derivatives, and aromatic metabolites. KEGG enrichment analysis revealed 20 significantly altered pathways, among which ABC transporters, amino acid biosynthesis, and the pentose phosphate pathway were identified as key metabolic routes. Conclusion Optimization of fermentation conditions for strain W71 significantly enhanced the antifungal activity of its fermentation broth against P. nicotianae and altered extracellular metabolic pathways, leading to substantial regulation of extracellular metabolite profiles.
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.7
Yuxuan Han,Yiyi Shao,Na Zhao,Zhiyan Wang,Rajamanikandan Sundarraj,Shuanghe Liu,Guoquan Fan,Qingquan Li,Chongxi Liu,Xiangjing Wang,Wensheng Xiang
Potato scab, caused by multiple Streptomyces species, is a major soil-borne disease with no effective chemical control. In this study, we isolated Streptomyces niveus NEAU-TZZ3 from the gut of Diestrammena japonica and identified its principal antibacterial metabolite as scabicidin. This compound exhibited potent inhibitory activity against six Streptomyces pathogens responsible for potato scab, with EC50 values of 0.056–0.84 μg/mL, substantially lower than those of the commercial bactericide zhongshengmycin. In pot and field trials, scabicidin provided dose-dependent control efficacy, reaching 81.7% and 52.03%, respectively. Mechanistic studies revealed that scabicidin targets the DNA gyrase GyrB subunit in Streptomyces scabies, competitively inhibiting ATP binding and disrupting DNA supercoiling. These findings establish scabicidin as a promising natural antibiotic from an insect-associated Streptomyces for effective potato scab management.
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高影响因子
3 Biotech
·
2021
·Vol. 12
·期 1
·1-12
·
IF 2.406
Zhang Dong,Ma Zhi,Chen Hanchi,Ma Weilin,Zhou Jiawei,Wang Qing,Min Chan,Lu Yuele,Chen Xiaolong
A novel strain with antifungal activity against Sclerotinia sclerotiorum was isolated from soil, and identified as Streptomyces sp. ZJUT-IFE-354 using morphological and 16S rDNA sequence analysis. The bioactive metabolite produced by strain ZJUT-IFE-354 was identified and characterized as valinomycin by spectroscopic and chemical methods. The yield of valinomycin was 191.26 mg/L from the culture of Streptomyces sp. ZJUT-IFE-354, which was the highest yield to our knowledge. The in vitro antifungal activity of valinomycin against S. sclerotiorum was investigated as 0.056 ± 0.012 (EC 50 ) and 0.121 ± 0.023 μg/mL (EC 95 ), respectively, which was approximately 10.696- and 30.960-fold more active than that of carbendazim. The results from scanning electron microscopy, cell membrane permeability, and D -sorbitol and ergosterol assay indicated that valinomycin exerted the antifungal activity probably by increasing permeability of fungal cell membrane, leading to mycelial electrolyte leakage, and eventually resulting in the death of S. sclerotiorum . Thus, valinomycin may be a promising antifungal agent to control S. sclerotiorum .
研究领域:
微生物学
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药理学
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植物病理学
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DOI
PubMed
高影响因子
Communications Biology
·
2019
·Vol. 2
·期 1
·1-9
·
IF 0
Gui Chun,Chen Jiang,Xie Qing,Mo Xuhua,Zhang Shanwen,Zhang Hua,Ma Junying,Li Qinglian,Gu Yu-Cheng,Ju Jianhua
Antibiotic-producing microorganism can develop strategies to deal with self-toxicity. Cytorhodins X and Y, cosmomycins A and B, and iremycin, are produced as final products from a marine-derived Streptomyces sp. SCSIO 1666. These C-7 reduced metabolites show reduced antimicrobial and comparable cytotoxic activities relative to their C-7 glycosylated counterparts. However, the biosynthetic mechanisms and relevant enzymes that drive C-7 reduction in cytorhodin biosynthesis have not yet been characterized. Here we report the discovery and characterization of a reductase, CytA, that mediates C-7 reduction of this anthracycline scaffold; CytA endows the producer Streptomyces sp. SCSIO 1666 with a means of protecting itself from the effects of its anthracycline products. Additionally, we identified cosmomycins C and D as two intermediates involved in cytorhodin biosynthesis and we also broadened the substrate specificity of CytA to clinically used anthracycline drugs.
研究领域:
微生物学
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生物化学
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药理学
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分子生物学
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DOI
PubMed
Marine Drugs
·
2024
·Vol. 22
·期 5
·212
·
IF 4.9
Xuejian Jiang,Hongjun Shu,Shuting Feng,Pinmei Wang,Zhizhen Zhang,Nan Wang
Naturally occurring echinocandin B and FR901379 are potent antifungal lipopeptides featuring a cyclic hexapeptide nucleus and a fatty acid side chain. They are the parent compounds of echinocandin drugs for the treatment of severe fungal infections caused by theCandidaandAspergillaspecies. To minimize hemolytic toxicity, the native fatty acid side chains in these drug molecules are replaced with designer acyl side chains. The deacylation of theN-acyl side chain is, therefore, a crucial step for the development and manufacturing of echinocandin-type antibiotics. Echinocandin E (ECE) is a novel echinocandin congener with enhanced stability generated via the engineering of the biosynthetic machinery of echinocandin B (ECB). In the present study, we report the discovery of the first echinocandin E acylase (ECEA) using the enzyme similarity tool (EST) for enzymatic function mining across protein families. ECEA is derived fromStreptomycessp. SY1965 isolated from a sediment collected from the Mariana Trench. It was cloned and heterologously expressed inS. lividansTK24. The resultant TKecea66 strain showed efficient cleavage activity of the acyl side chain of ECE, showing promising applications in the development of novel echinocandin-type therapeutics. Our results also provide a showcase for harnessing the essentially untapped biodiversity from the hadal ecosystems for the discovery of functional molecules.
研究领域:
微生物学
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药学
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生物技术
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海洋生物学
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酶学
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PubMed
高影响因子
Catalysts
·
2020
·Vol. 10
·期 9
·1057
·
IF 3.52
Jing Wang,Sheng Xu,Yang Pang,Xin Wang,Kequan Chen,Pingkai Ouyang
To achieve efficient bio-production of phospholipase D (PLD), PLDs from different organisms were expressed inE.coli. An efficient secretory expression system was thereby developed for PLD. First, PLDs fromStreptomycesPMF andStreptomyces racemochromogeneswere separately over-expressed inE.colito compare their transphosphatidylation activity based on the synthesis of phosphatidylserine (PS), and PLDPMFwas determined to have higher activity. To further improve PLDPMFsynthesis, a secretory expression system suitable for PLDPMFwas constructed and optimized with different signal peptides. The highest secretory efficiency was observed when the PLD * (PLDPMFwith the native signal peptide Nat removed) was expressed fused with the fusion signal peptide PelB-Nat inE. coli. The fermentation conditions were also investigated to increase the production of recombinant PLD and 10.5 U/mL PLD was ultimately obtained under the optimized conditions. For the application of recombinant PLD to PS synthesis, the PLD properties were characterized and 30.2 g/L of PS was produced after 24 h of bioconversion when 50 g/L phosphatidylcholine (PC) was added.Keywords:phospholipase D;phosphatidylserine;secretory expression;enzymatic catalysis
研究领域:
生物化学
·
分子生物学
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2022
·Vol. 24
·期 1
·275
·
IF 6.208
Fei Li,Honglu Zhao,Yuxin Liu,Jiaqi Zhang,Hongbo Yu
Lytic polysaccharide monooxygenases (LPMOs) have the potential to improve recalcitrant polysaccharide hydrolysis by the oxidizing cleavage of glycosidic bond.Streptomycesspecies are major chitin decomposers in soil ecological environments and encode multiplelpmogenes. In this study, we demonstrated that transcription of thelpmogene,Sclpmo10G, in theStreptomyces coelicolorA3(2) (ScA3(2)) strain is strongly induced by chitin. TheScLPMO10G protein was further expressed inEscherichia coliand characterized in vitro. TheScLPMO10G protein showed oxidation activity towards chitin. Chitinase synergy experiments demonstrated that the addition ofScLPMO10G resulted in a substantial in vitro increase in the reducing sugar levels. Moreover, in vivo the LPMO-overexpressing strainScΔLPMO10G(+) showed stronger chitin-degrading ability than the wild-type, leading to a 2.97-fold increase in reducing sugar level following chitin degradation. The total chitinase activity ofScΔLPMO10G(+) was 1.5-fold higher than that ofScA3(2). In summary,ScLPMO10G may play a role in chitin biodegradation inS. coelicolor, which could have potential applications in biorefineries.Keywords:lytic polysaccharide monooxygenases;transcription;expression;Streptomyces coelicolorA3(2);chitin biodegradation
研究领域:
微生物学
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生物化学
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DOI
PubMed
高影响因子
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