Ansamitocin derivative TN-006
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| Category | Mycotoxins |
| Catalog number | BBF-05708 |
| CAS | 72902-38-6 |
| Molecular Weight | 621.1 |
| Molecular Formula | C31H41ClN2O9 |
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Description
Ansamitocin derivative TN-006 is a derivative of Ansamitocin, a family of polyketide antibiotics comprising a naphthalene/benzene or napthaquinone/benzoquinone ring system bridged at nonadjacent positions by an aliphatic chain.
Specification
| Synonyms | PDM3 |
| IUPAC Name | [(1S,2R,3S,5S,6S,16E,18E,20R,21S)-11-chloro-12,21-dihydroxy-20-methoxy-2,5,9,16-tetramethyl-8,23-dioxo-4,24-dioxa-9,22-diazatetracyclo[19.3.1.110,14.03,5]hexacosa-10,12,14(26),16,18-pentaen-6-yl] 2-methylpropanoate |
| Canonical SMILES | CC1C2CC(C(C=CC=C(CC3=CC(=C(C(=C3)O)Cl)N(C(=O)CC(C4(C1O4)C)OC(=O)C(C)C)C)C)OC)(NC(=O)O2)O |
| InChI | InChI=1S/C31H41ClN2O9/c1-16(2)28(37)42-24-14-25(36)34(6)20-12-19(13-21(35)26(20)32)11-17(3)9-8-10-23(40-7)31(39)15-22(41-29(38)33-31)18(4)27-30(24,5)43-27/h8-10,12-13,16,18,22-24,27,35,39H,11,14-15H2,1-7H3,(H,33,38)/b10-8+,17-9+/t18-,22+,23-,24+,27+,30+,31+/m1/s1 |
| InChI Key | YQVKSZNVVCIETH-PRWXLFGZSA-N |
Reference Reading
1. 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.
2. 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.
3. Natural Products Mediated Targeting of Virally Infected Cancer
Iram Fatima, Sobia Kanwal, Tariq Mahmood Dose Response. 2019 Jan 8;17(1):1559325818813227. doi: 10.1177/1559325818813227. eCollection 2019 Jan-Mar.
The role of viral infection in developing cancer was determined in the start of 20th century. Until now, 8 different virus-associated cancers have been discovered and most of them progressed in immunosuppressed individuals. The aim of the present study is to look into the benefits of natural products in treating virally infected cancers. The study focuses on bioactive compounds derived from natural sources. Numerous pharmaceutical agents have been identified from plants (vincristine, vinblastine, stilbenes, combretastatin, and silymarin), marine organisms (bryostatins, cephalostatin, ecteinascidins, didemnin, and dolastatin), insects (cantharidin, mastoparan, parectadial, and cecropins), and microorganisms (vancomycin, rhizoxin, ansamitocins, mitomycin, and rapamycin). Beside these, various compounds have been observed from fruits and vegetables which can be utilized in anticancer therapy. These include curcumin in turmeric, resveratrol in red grapes, S-allyl cysteine in allium, allicin in garlic, catechins in green tea, and β-carotene in carrots. The present study addresses various types of virally infected cancers, their mechanism of action, and the role of different cell surface molecules elicited during viral binding and entry into the target cell along with the anticancer drugs derived from natural products by targeting screening of bioactive compounds from natural sources.
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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 ╳
