Ansamitocin PHO-0
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
| Category | Antibiotics |
| Catalog number | BBF-00473 |
| CAS | 79082-29-4 |
| Molecular Weight | 581.05 |
| Molecular Formula | C28H37N2O9Cl |
Online Inquiry
Description
It is produced by the strain of Streptamyces sclerotialus, Str. flavochromogenes, Str. flaviscleroticus, Str. luridus, Chainia nigra, Strertosporangium roseurn, Nocardia sp. N-1231. It has antiprotozoal and antitumor activity.
Specification
| Synonyms | Maytansine, 3-O-de[2-(acetylmethylamino)-1-oxopropyl]-15-hydroxy-, (15R)-; (15R)-3-O-De[2-(acetylmethylamino)-1-oxopropyl]-15-hydroxymaytansine; 4,24-Dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosane, maytansine deriv.; Antibiotic C 15003PHO0 |
Properties
| Antibiotic Activity Spectrum | neoplastics (Tumor); parasites |
| Boiling Point | 873.3±65.0 °C |
| Density | 1.390±0.10 g/cm3 |
| Solubility | Soluble in Mthanol, Chloroform; Poorly soluble in Water, Hexane |
Reference Reading
1. Global Regulator AdpA_1075 Regulates Morphological Differentiation and Ansamitocin Production in Actinosynnema pretiosum subsp. auranticum
Siyu Guo, Tingting Leng, Xueyuan Sun, Jiawei Zheng, Ruihua Li, Jun Chen, Fengxian Hu, Feng Liu, Qiang Hua Bioengineering (Basel). 2022 Nov 21;9(11):719. doi: 10.3390/bioengineering9110719.
Actinosynnema pretiosum is a well-known producer of maytansinoid antibiotic ansamitocin P-3 (AP-3). Growth of A. pretiosum in submerged culture was characterized by the formation of complex mycelial particles strongly affecting AP-3 production. However, the genetic determinants involved in mycelial morphology are poorly understood in this genus. Herein a continuum of morphological types of a morphologically stable variant was observed during submerged cultures. Expression analysis revealed that the ssgA_6663 and ftsZ_5883 genes are involved in mycelial aggregation and entanglement. Combing morphology observation and morphology engineering, ssgA_6663 was identified to be responsible for the mycelial intertwining during liquid culture. However, down-regulation of ssgA_6663 transcription was caused by inactivation of adpA_1075, gene coding for an AdpA-like protein. Additionally, the overexpression of adpA_1075 led to an 85% increase in AP-3 production. Electrophoretic mobility shift assays (EMSA) revealed that AdpA_1075 may bind the promoter regions of asm28 gene in asm gene cluster as well as the promoter regions of ssgA_6663. These results confirm that adpA_1075 plays a positive role in AP-3 biosynthesis and morphological differentiation.
2. Metabolomic change and pathway profiling reveal enhanced ansamitocin P-3 production in Actinosynnema pretiosum with low organic nitrogen availability in culture medium
Ting Liu, Linbing Yang, Jun Chen, Fengxian Hu, Liu-Jing Wei, Qiang Hua Appl Microbiol Biotechnol. 2020 Apr;104(8):3555-3568. doi: 10.1007/s00253-020-10463-9. Epub 2020 Feb 29.
Ansamitocin P-3 (AP-3), a 19-membered polyketide macrocyclic lactam, has potent antitumor activity. Our previous study showed that a relatively low organic nitrogen concentration in culture medium could significantly improve AP-3 production of Actinosynnema pretiosum. In the present study, we aimed to reveal the possible reasons for this improvement through metabolomic and gene transcriptional analytical methods. At the same time, a metabolic pathway profile based on metabolome data and pathway correlation information was performed to obtain a systematic view of the metabolic network modulations of A. pretiosum. Orthogonal partial least squares discriminant analysis showed that nine and eleven key metabolites directly associated with AP-3 production at growth phase and ansamitocin production phase, respectively. In-depth pathway analysis results highlighted that low organic nitrogen availability had significant impacts on central carbon metabolism and amino acid metabolic pathways of A. pretiosum and these metabolic responses were found to be beneficial to precursor supply and ansamitocin biosynthesis. Furthermore, real-time PCR results showed that the transcription of genes involved in precursor and ansamitocin biosynthetic pathways were remarkably upregulated under low organic nitrogen condition thus directing increased carbon flux toward ansamitocin biosynthesis. More importantly, the metabolic pathway analysis demonstrated a competitive relationship between fatty acid and AP-3 biosynthesis could significantly affect the accumulation of AP-3. Our findings provided new knowledge on the organic nitrogen metabolism and ansamitocin biosynthetic precursor in A. pretiosum and identified several important rate-limiting steps involved in ansamitocin biosynthesis thus providing a theoretical basis of further improvement in AP-3 production.
3. Efflux identification and engineering for ansamitocin P-3 production in Actinosynnema pretiosum
Xinran Wang, Jianhua Wei, Yifan Xiao, Shuhui Luan, Xinjuan Ning, Linquan Bai Appl Microbiol Biotechnol. 2021 Jan;105(2):695-706. doi: 10.1007/s00253-020-11044-6. Epub 2021 Jan 4.
Ansamitocin P-3 (AP-3) exhibits potent biological activities against various tumor cells. As an important drug precursor, reliable supply of AP-3 is limited by low fermentation yield. Although different strategies have been implemented to improve AP-3 yield, few have investigated the impact of efflux on AP-3 production. In this study, AP-3 efflux genes were identified through combined analysis of two sets of transcriptomes. The production-based transcriptome was implemented to search for efflux genes highly expressed in response to AP-3 accumulation during the fermentation process, while the resistance-based transcriptome was designed to screen for genes actively expressed in response to the exogenous supplementation of AP-3. After comprehensive analysis of two transcriptomes, six efflux genes outside the ansamitocin BGC were identified. Among the six genes, individual deletion of APASM_2704, APASM_6861, APASM_3193, and APASM_2805 resulted in decreased AP-3 production, and alternative overexpression led to AP-3 yield increase from 264.6 to 302.4, 320.4, 330.6, and 320.6 mg/L, respectively. Surprisingly, APASM_2704 was found to be responsible for exportation of AP-3 and another macro-lactam antibiotic pretilactam. Furthermore, growth of APASM_2704, APASM_3193, or APASM_2805 overexpression mutants was obviously improved under 300 mg/L AP-3 supplementation. In summary, our study has identified AP-3 efflux genes outside the ansamitocin BGC by comparative transcriptomic analysis, and has shown that enhancing the transcription of transporter genes can improve AP-3 production, shedding light on strategies used for exporter screening and antibiotic production improvement. KEY POINTS: · AP-3-related efflux genes were identified by transcriptomic analysis. · Deletion of the identified efflux genes led in AP-3 yield decrease. · Overexpression of the efflux genes resulted in increased AP-3 production.
Recommended Products
| BBF-01826 | Deoxymannojirimycin | Inquiry |
| BBF-02614 | Nystatin | Inquiry |
| BBF-01693 | Doxorubicin EP Impurity A (Daunorubicin) | Inquiry |
| BBF-02642 | Lactonamycin | Inquiry |
| BBF-01829 | Deoxynojirimycin | Inquiry |
| BBF-01825 | Loganin | Inquiry |
Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
