Mycinamicin I
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
| Category | Antibiotics |
| Catalog number | BBF-01968 |
| CAS | 73665-15-3 |
| Molecular Weight | 711.88 |
| Molecular Formula | C37H61NO12 |
Online Inquiry
Description
Mycinamicin I is a macrolide antibiotic produced by Micromonospora griseorubida sp. nov. Activity against gram-positive bacteria.
Specification
| Synonyms | Mycinomycin I; Antibiotic A 11725 I; Antibiotic AR 5-1 |
| IUPAC Name | (2R,3R,6E,8S,9S,10S,12R,14E)-9-[(2S,3R,4S,6R)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-3-ethyl-2-[[(2R,3R,4R,5R,6R)-5-hydroxy-3,4-dimethoxy-6-methyloxan-2-yl]oxymethyl]-8,10,12-trimethyl-4,17-dioxabicyclo[14.1.0]heptadeca-6,14-diene-5,13-dione |
| Canonical SMILES | CCC1C(C2C(O2)C=CC(=O)C(CC(C(C(C=CC(=O)O1)C)OC3C(C(CC(O3)C)N(C)C)O)C)C)COC4C(C(C(C(O4)C)O)OC)OC |
| InChI | InChI=1S/C37H61NO12/c1-11-27-24(18-45-37-35(44-10)34(43-9)30(41)23(6)47-37)33-28(49-33)14-13-26(39)20(3)16-21(4)32(19(2)12-15-29(40)48-27)50-36-31(42)25(38(7)8)17-22(5)46-36/h12-15,19-25,27-28,30-37,41-42H,11,16-18H2,1-10H3/b14-13+,15-12+/t19-,20+,21-,22+,23+,24+,25-,27+,28?,30+,31+,32+,33?,34+,35+,36-,37+/m0/s1 |
| InChI Key | QABCJBNUVVMWAL-HXRJSAKRSA-N |
Properties
| Antibiotic Activity Spectrum | Gram-positive bacteria |
| Boiling Point | 814.8°C at 760 mmHg |
| Melting Point | 103-107°C |
| Density | 1.19 g/cm3 |
Reference Reading
1. Biochemical and Structural Characterization of MycCI, a Versatile P450 Biocatalyst from the Mycinamicin Biosynthetic Pathway
Matthew D DeMars nd, Fang Sheng, Sung Ryeol Park, Andrew N Lowell, Larissa M Podust, David H Sherman ACS Chem Biol. 2016 Sep 16;11(9):2642-54. doi: 10.1021/acschembio.6b00479. Epub 2016 Aug 5.
Cytochrome P450 monooxygenases (P450s) are some of nature's most ubiquitous and versatile enzymes for performing oxidative metabolic transformations. Their unmatched ability to selectively functionalize inert C-H bonds has led to their increasing employment in academic and industrial settings for the production of fine and commodity chemicals. Many of the most interesting and potentially biocatalytically useful P450s come from microorganisms, where they catalyze key tailoring reactions in natural product biosynthetic pathways. While most of these enzymes act on structurally complex pathway intermediates with high selectivity, they often exhibit narrow substrate scope, thus limiting their broader application. In the present study, we investigated the reactivity of the P450 MycCI from the mycinamicin biosynthetic pathway toward a variety of macrocyclic compounds and discovered that the enzyme exhibits appreciable activity on several 16-membered ring macrolactones independent of their glycosylation state. These results were corroborated by performing equilibrium substrate binding experiments, steady-state kinetics studies, and X-ray crystallographic analysis of MycCI bound to its native substrate mycinamicin VIII. We also characterized TylHI, a homologous P450 from the tylosin pathway, and showed that its substrate scope is severely restricted compared to MycCI. Thus, the ability of the latter to hydroxylate both macrocyclic aglycones and macrolides sets it apart from related biosynthetic P450s and highlights its potential for developing novel P450 biocatalysts with broad substrate scope and high regioselectivity.
2. Total Synthesis of Mycinamicin IV as Integral Part of a Collective Approach to Macrolide Antibiotics
Georg Späth, Alois Fürstner Chemistry. 2022 Feb 19;28(11):e202104400. doi: 10.1002/chem.202104400. Epub 2022 Jan 10.
The total synthesis of the 16-membered macrolide mycinamicin IV is outlined, which complements our previously disclosed, largely catalysis-based route to the aglycone. This work must also be seen in the context of our recent conquest of aldgamycin N, a related antibiotic featuring a similar core but a distinctly different functionalization pattern. Taken together, these projects prove that the underlying blueprint is integrative and hence qualifies for a collective approach to this prominent class of natural products. In both cases, the final glycosylation phase mandated close attention and was accomplished only after robust de novo syntheses of the (di)deoxy sugars of the desosamine, chalcose, mycinose and aldgarose types had been established. Systematic screening of the glycosidation promoter was also critically important for success.
3. Engineering sequence and selectivity of late-stage C-H oxidation in the MycG iterative cytochrome P450
Yohei Iizaka, Ryusei Arai, Akari Takahashi, Mikino Ito, Miho Sakai, Atsushi Fukumoto, David H Sherman, Yojiro Anzai J Ind Microbiol Biotechnol. 2022 Jan 20;49(1):kuab069. doi: 10.1093/jimb/kuab069.
MycG is a multifunctional P450 monooxygenase that catalyzes sequential hydroxylation and epoxidation or a single epoxidation in mycinamicin biosynthesis. In the mycinamicin-producing strain Micromonospora griseorubida A11725, very low-level accumulation of mycinamicin V generated by the initial C-14 allylic hydroxylation of MycG is observed due to its subsequent epoxidation to generate mycinamicin II, the terminal metabolite in this pathway. Herein, we investigated whether MycG can be engineered for production of the mycinamicin II intermediate as the predominant metabolite. Thus, mycG was subject to random mutagenesis and screening was conducted in Escherichia coli whole-cell assays. This enabled efficient identification of amino acid residues involved in reaction profile alterations, which included MycG R111Q/V358L, W44R, and V135G/E355K with enhanced monohydroxylation to accumulate mycinamicin V. The MycG V135G/E355K mutant generated 40-fold higher levels of mycinamicin V compared to wild-type M. griseorubida A11725. In addition, the E355K mutation showed improved ability to catalyze sequential hydroxylation and epoxidation with minimal mono-epoxidation product mycinamicin I compared to the wild-type enzyme. These approaches demonstrate the ability to selectively coordinate the catalytic activity of multifunctional P450s and efficiently produce the desired compounds.
Recommended Products
| BBF-01825 | Loganin | Inquiry |
| BBF-01826 | Deoxymannojirimycin | Inquiry |
| BBF-05862 | Epirubicin | Inquiry |
| BBF-01693 | Doxorubicin EP Impurity A (Daunorubicin) | Inquiry |
| BBF-03753 | Baicalin | Inquiry |
| BBF-03755 | Actinomycin D | 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 ╳
