Effects of mycosubtilin homolog algicides from a marine bacterium, Bacillus sp. SY-1, against the harmful algal bloom species Cochlodinium polykrikoides

4区 · 生物学

Article

作者: Jeong, Seong-Yun ; Son, Hong-Joo

The marine bacterium, Bacillus sp. SY-1, produced algicidal compounds that are notably active against the bloom-forming alga Cochlodinium polykrikoides. We isolated three algicidal compounds and identified these as mycosubtilins with molecular weights of 1056, 1070, and 1084 (designated MS 1056, 1070, and 1084, respectively), based on amino acid analyses and ¹H, ¹³C, and two-dimensional nuclear magnetic resonance spectroscopy, including ¹H-¹⁵N heteronuclear multiple bond correlation analysis. MS 1056 contains a β-amino acid residue with an alkyl side chain of C₁₅, which has not previously been seen in known mycosubtilin families. MS 1056, 1070, and 1084 showed algicidal activities against C. polykrikoides with 6-h LC₅₀ values of 2.3 ± 0.4, 0.8 ± 0.2, and 0.6 ± 0.1 μg/ml, respectively. These compounds also showed significant algicidal activities against other harmful algal bloom species. In contrast, MS 1084 showed no significant growth inhibitory effects against other organisms, including bacteria and microalgae, although does inhibit the growth of some fungi and yeasts. These observations imply that the algicidal bacterium Bacillus sp. SY-1 and its algicidal compounds could play an important role in regulating the onset and development of harmful algal blooms in natural environments.

2014-07-18·ACS chemical biology2区 · 生物学

Semisynthesis of SY-1 for Investigation of Breast Cancer Stem Cell Selectivity of C-Ring-Modified Salinomycin Analogues

2区 · 生物学

Article

作者: Borgström, Björn ; Hegardt, Cecilia ; Strand, Daniel ; Huang, Xiaoli ; Persson, Lo ; Oredsson, Stina ; Månsson, Linda

Salinomycin, a naturally occurring polyether ionophore was recently found to selectively reduce the proportion of CD44(+)/CD24(-) cells, a phenotype associated with breast cancer stem cells. Subsequent studies from our group showed that chemical modification of the allylic C20 hydroxyl of salinomycin, located at the C-ring, can enhance the activity of derivatives against breast cancer cells over 5-fold compared to the native structure. Access to C-ring-modified salinomycin analogues is thus of interest from both a mechanistic and a synthetic perspective. Here, we report efficient strategies for gram scale synthesis of the natural product SY-1 (20-deoxy salinomycin), and a saturated analogue, 18,19-dihydro SY-1, for a comparative in vitro investigation of the biological profiles of these compounds with that of salinomycin. Across several assays, the deoxygenated structures required higher concentrations to elicit similar cellular responses to that of salinomycin. Similarly to salinomycin, SY-1 or 18,19-dihydro SY-1 treatment was found to reduce the proportion of CD44(+)/CD24(-) cells with essentially complete selectivity up to ∼IC25. Importantly, the proportion of CD44(+)/CD24(-) cells showed a pronounced U-shaped dose response curve for salinomycin and its derivatives, but not for paclitaxel. The concentration for maximum response in this assay followed differences in IC50 for salinomycin and its analogues, which emphasizes the importance of taking concentration dependence into account when comparing effects on the CD44(+)/CD24(-) phenotype. Small differences in the global conformation within the triad of compounds investigated together with differences in activity across assays emphasize the importance of substitution at C20 for the activity of salinomycin and its derivatives.

PeerJ3区 · 生物学

Exploring the genome of Lactobacillaceae spp. Sy-1 isolated from Heterotrigona itama honey

3区 · 生物学

ArticleOA

作者: Abdul Wahab, Roswanira ; Huyop, Fahrul ; Huda, Nurul ; Misson, Mailin ; Syed Yaacob, Syariffah Nuratiqah

Background:

Honey produced by Heterotrigona itama is highly preferred among consumers due to its high-value as a functional food and beneficial lactic acid bacteria (LAB) reservoir. Fructophilic lactic acid bacteria (FLAB) are a group of LAB with unique growth characteristics and are regarded as promising producers of bioactive compounds. Hence, it is not surprising that LAB, especially FLAB, may be involved with the excellent bioactivity of H. itama honey. With the trending consumer preference for H. itama honey coupled with increasing awareness for healthy food, the genomic background of FLAB isolated from this honey must, therefore, be clearly understood. In this study, one FLAB strain designated as Sy-1 was isolated from freshly collected H. itama honey. Its FLAB behavior and genomic features were investigated to uncover functional genes that could add value to functional food.

Methods:

The fructophilic characteristics of strain Sy-1 were determined, and the genome was sequenced using Illumina iSeq100 and Oxford Nanopore. The average nucleotide identity and phylogenetic analyses based on 16S rRNA, 92 core genes, and whole-genome sequence were performed to unravel the phylogenetic position of strain Sy-1. NCBI Prokaryotic Genome Annotation Pipeline annotated the genome, while the EggNOG-mapper, BLASTKoala, and GHOSTKoala were used to add functional genes and pathways information.

Results:

Strain Sy-1 prefers D-fructose over D-glucose and actively metabolizes D-glucose in the presence of electron acceptors. Genomic annotation of strain Sy-1 revealed few genes involved in carbohydrate transport and metabolism, and partial deletion of adhE gene, in line with the characteristic of FLAB. The 16S rRNA gene sequence of strain Sy-1 showed the highest similarity to unknown LAB species isolated from the gut of honeybees. The phylogenetic analyses discovered that strain Sy-1 belonged to the Lactobacillaceae family and formed a separate branch closer to type strain from the genera of Acetilactobacillus and Apilactobacillus. The ANI analysis showed the similarity of the closest relative, Apilactobacillus micheneri Hlig3T. The assembled genome of Sy-1 contains 3 contigs with 2.03 Mbp and a 41% GC content. A total of 1,785 genes were identified, including 1,685 protein-coding genes, 68 tRNA, and 15 rRNA. Interestingly, strain Sy-1 encoded complete genes for the biosynthesis of folate and riboflavin. High-performance liquid chromatography analysis further confirmed the high production of folic acid (1.346 mg/L) by Sy-1.

Discussion:

Based on phylogenetic and biochemical characteristics, strain Sy-1 should be classified as a novel genus in the family of Lactobacillaceae and a new member of FLAB. The genome information coupled with experimental studies supported the ability of strain Sy-1 to produce high folic acid. Our collective findings support the suitable application of FLAB strain Sy-1 in the functional food and pharmaceutical industries.

项与 SY-001 相关的新闻（医药）

2023-12-20

·PRNewswire

CellOrigin announced treatment of the first patient with CAR-M in China and reported the second generation of CAR-M for solid tumors

HANGZHOU, China, Dec. 20, 2023 /PRNewswire/ -- Recently, a CAR-macrophage therapy product (CAR-M) SY001 from CellOrigin Biotechnology (Hangzhou) Co., Ltd. was dosed to the first patient in a hospital in China. "A single center, single-arm, dose-escalation, exploratory clinical trial to examine the safety, tolerability, pharmacokinetics and preliminary efficacy of SY001 from CellOrigin Biotechnology in patients with advanced solid tumors" is the first investigator-initiated clinical study of CAR-M cell therapy product in China. The successful completion of the first patient dosing of SY001 demonstrates the advanced technology of the company's R&D platform and the maturity of the CMC platform. Currently, the clinical study is actively recruiting patients. SY001 was well tolerated and no dose-limiting toxicity (DLT) was observed (n=2). Only 2 grade 3 adverse events occurred; Common grade 1 - 2 adverse events included fever, elevated C-reactive protein, etc. No cytokine release syndrome or neurotoxicity related to cell infusion occurred in any patients. The clinical data of CAR-M products up to now suggest the excellent safety and certain clinical benefits of macrophage immunotherapy. CellOrigin expects that this innovative product will prove its safety and effectiveness in clinical trials, bringing new hope for the treatment of solid tumors, thereby improving patients' quality of life and prolonging their life span. Besides, in November 2023, CellOrigin collaborated with Zhejiang University to publish a paper entitled "A second generation M1-polarized CAR macrophage with antitumor efficacy" in Nature immunology, designing an exclusive CAR with antigen-dependent polarization and activation of macrophage function (TIR-CAR or M-CAR) by introducing the TIR signal transduction domain. Based on M-CAR, a functionally enhanced second generation CAR-iMAC has been developed to enhance the effectiveness of the therapy for solid tumors. The mechanism of antigen-dependent activation and polarization of the second generation CAR-iMAC and the mechanisms of solid tumor cell killing were also revealed. In November 2020, the team published a paper in J Hematol Oncol entitled "Pluripotent stem cell-derived CAR-macrophage cells with antigen-dependent anti-cancer cell functions." It opens the door for human iPSC-derived CAR-macrophage (CAR-iMAC) and its applications in targeted anti-tumor research. The first generation CAR-iMAC was designed, and was capable of carrying out the antigen-dependent killing of tumor cells. On September 11, 2023, the team collaborated with Dr. Wang Ben's Research Group of Zhejiang University to publish a paper entitled "Targeted glycan degradation potentials cellular immunotherapy for solid tumors" in Proceedings of the National Academy of Sciences (PNAS). The collaboration found that simultaneous deletion of sialidase-binding immune checkpoints Siglec-5 and Siglec-10 (DKO-CAR-iMac) on macrophages significantly enhanced CAR-iMAC's anti-solid tumor function. Almost the same time, the team published another paper entitled "Metabolic Reprogramming via ACOD1 depletion enhances function of human induced pluripotent stem cell-derived CAR-macrophases in solid tumors" in Nature communications. A CRISPR Screen method was used to find the key metabolic genes related to CAR-iMAC polarization in tumor microenvironment. It was discovered that knockout of ACOD1 (or IRG1) could improve macrophage proinflammatory polarization, phagocytic capacity and tumor-killing activity. Furthermore, the study also found that the anti-tumor effect of ACOD1-/- MSLN-CAR-iMAC can be further enhanced by combining immune checkpoint inhibitors. These findings offer fresh concepts for remodeling macrophages based on metabolic reprogramming or editing the immune checkpoints. Based on these research results, CellOrigin is conducting a series of pre-clinical and clinical studies of CAR-macrophage therapies for solid tumors in an effort to provide patients with safe and effective treatment choices as soon as possible. About CellOrigin: CellOrigin is committed to the development and clinical translation of their proprietary CAR-expressing iPSC-derived immune cells such as CAR-iMAC. They have obtained engineered immune cells derived from iPSC using cutting-edge technologies including gene editing and synthetic biology. CellOrigin takes advantage of the unique characteristics of macrophages that can infiltrate the solid tumor microenvironment (TME), and is developing CAR-M products mainly for relapsed/refractory solid tumors. They have completed the establishment of a clinical-grade iPSC cell bank, independently developed the CMC process of CAR-iMAC cells that can be produced in large scale to meet the amount for off-the-shelf products, and established a complete GMP quality system and corresponding quality control methods. They are collaborating with domestic and international hospitals for clinical trials, and also seeking for opportunities of licensing of the technology platform and certain pipelines. For more information,please contact Yaoyao Li, [email protected]. SOURCE CellOrigin

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