Bu-2545
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Category | Antibiotics |
Catalog number | BBF-03268 |
CAS | 75007-09-9 |
Molecular Weight | 378.48 |
Molecular Formula | C16H30N2O6S |
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Description
Bu-2545 is a lincomycin-azicillin antibiotic produced by Streptomyces No.H2305. Activity against Gram-positive bacteria.
Specification
Synonyms | D-erythro-alpha-D-galacto-Octopyranoside, methyl 6,8-dideoxy-7-O-methyl-6-(((1-methyl-2-pyrrolidinyl)carbonyl)amino)-1-thio-, (S)- |
IUPAC Name | N-[2-methoxy-1-(3,4,5-trihydroxy-6-methylsulfanyloxan-2-yl)propyl]-1-methylpyrrolidine-2-carboxamide |
Canonical SMILES | CC(C(C1C(C(C(C(O1)SC)O)O)O)NC(=O)C2CCCN2C)OC |
InChI | InChI=1S/C16H30N2O6S/c1-8(23-3)10(17-15(22)9-6-5-7-18(9)2)14-12(20)11(19)13(21)16(24-14)25-4/h8-14,16,19-21H,5-7H2,1-4H3,(H,17,22) |
InChI Key | WVXCVWNSJUNIRQ-UHFFFAOYSA-N |
Properties
Appearance | Powder |
Antibiotic Activity Spectrum | Gram-positive bacteria |
Boiling Point | 606.0±55.0°C at 760 mmHg |
Density | 1.3±0.1 g/cm3 |
Solubility | Soluble in Methanol |
Reference Reading
1. Differences in PLP-Dependent Cysteinyl Processing Lead to Diverse S-Functionalization of Lincosamide Antibiotics
Min Wang, Qunfei Zhao, Qinglin Zhang, Wen Liu J Am Chem Soc. 2016 May 25;138(20):6348-51. doi: 10.1021/jacs.6b01751. Epub 2016 May 16.
Pyridoxal-5'-phosphate (PLP)-dependent proteins constitute one of the largest and most important families of enzymes in living organisms. These proteins participate in numerous biochemical processes, many of which have not been characterized, and transform substrates containing an amino group through various reactions that share aldimine as a common intermediate. Herein, we report that the PLP-dependent enzymes CcbF and LmbF, which are highly related in phylogenesis, process cysteine S-conjugated intermediates in different ways and associate with individual downstream enzyme(s) toward distinct S-functionalization of the lincosamide antibiotics celesticetin and lincomycin A. CcbF catalyzes an unusual conversion that involves decarboxylation-coupled oxidative deamination of the cysteinyl group during the formation of a two-carbon alcohol linker, whereas LmbF is responsible for β-elimination, followed by S-methylation to produce a methylmercapto group. The two tailoring routes are variable and exchangeable with each other, allowing for in vitro combinatorial biosynthesis of a number of hybrid lincosamide antibiotics, including the natural product Bu-2545. These findings demonstrate the wide diversity of PLP chemistry in enzymatic catalysis and its promising applicability in creation of new molecules.
2. Biosynthesis of Lincosamide Antibiotics: Reactions Associated with Degradation and Detoxification Pathways Play a Constructive Role
Daozhong Zhang, Zhijun Tang, Wen Liu Acc Chem Res. 2018 Jun 19;51(6):1496-1506. doi: 10.1021/acs.accounts.8b00135. Epub 2018 May 24.
Natural products typically are small molecules produced by living organisms. These products possess a wide variety of biological activities and thus have historically played a critical role in medicinal chemistry and chemical biology either as chemotherapeutic agents or as useful tools. Natural products are not synthesized for use by human beings; rather, living organisms produce them in response to various biochemical processes and environmental concerns, both internal and external. These processes/concerns are often dynamic and thus motivate the diversification, optimization, and selection of small molecules in line with changes in biological function. Consequently, the interactions between living organisms and their environments serve as an engine that drives coevolution of natural products and their biological functions and ultimately programs the constant theme of small-molecule development in nature based on biosynthesis generality and specificity. Following this theme, we herein review the biosynthesis of lincosamide antibiotics and dissect the process through which nature creates an unusual eight-carbon aminosugar (lincosamide) and then functionalizes this common high-carbon chain-containing sugar core with diverse l-proline derivatives and sulfur appendages to form individual members, including the clinically useful anti-infective agent lincomycin A and its naturally occurring analogues celesticetin and Bu-2545. The biosynthesis of lincosamide antibiotics is unique in that it results from an intersection of anabolic and catabolic chemistry. Many reactions that are usually involved in degradation and detoxification play a constructive role in biosynthetic processes. Formation of the trans-4-propyl-l-proline residue in lincomycin A biosynthesis requires an oxidation-associated degradation-like pathway composed of heme peroxidase-catalyzed ortho-hydroxylation and non-heme 2,3-dioxygenase-catalyzed extradiol cleavage for l-tyrosine processing prior to the building-up process. Mycothiol (MSH) and ergothioneine (EGT), two small-molecule thiols that are known for their redox-relevant roles in protection against various endogenous and exogenous stresses, function through two unusual S-glycosylations to mediate an eight-carbon aminosugar transfer, activation, and modification during the molecular assembly and tailoring processes in lincosamide antibiotic biosynthesis. Related intermediates include an MSH S-conjugate, mercapturic acid, and a thiomethyl product, which are reminiscent of intermediates found in thiol-mediated detoxification metabolism. In these biosynthetic pathways, "old" protein folds can result in "new" enzymatic activity, such as the DinB-2 fold protein for thiol exchange between EGT and MSH, the γ-glutamyltranspeptidase homologue for C-C bond cleavage, and the pyridoxal-5'-phosphate-dependent enzyme for diverse S-functionalization, generating interest in how nature develops remarkably diverse biochemical functions using a limited range of protein scaffolds. These findings highlight what we can learn from natural product biosynthesis, the recognition of its generality and specificity, and the natural theme of the development of bioactive small molecules, which enables the diversification process to advance and expand small-molecule functions.
3. Characterization of Enzymes Catalyzing Transformations of Cysteine S-Conjugated Intermediates in the Lincosamide Biosynthetic Pathway
Richiro Ushimaru, Chia-I Lin, Eita Sasaki, Hung-Wen Liu Chembiochem. 2016 Sep 2;17(17):1606-11. doi: 10.1002/cbic.201600223. Epub 2016 Jul 19.
Lincosamides such as lincomycin A, celesticetin, and Bu-2545, constitute an important group of antibiotics. These natural products are characterized by a thiooctose linked to a l-proline residue, but they differ with regards to modifications of the thioacetal moiety, the pyrrolidine ring, and the octose core. Here we report that the pyridoxal 5'-phosphate-dependent enzyme CcbF (celesticetin biosynthetic pathway) is a decarboxylating deaminase that converts a cysteine S-conjugated intermediate into an aldehyde. In contrast, the homologous enzyme LmbF (lincomycin biosynthetic pathway) catalyzes C-S bond cleavage of the same intermediate to afford a thioglycoside. We show that Ccb4 and LmbG (downstream methyltransferases) convert the aldehyde and thiol intermediates into a variety of methylated lincosamide compounds including Bu-2545. The substrates used in these studies are the β-anomers of the natural substrates. The findings not only provide insight into how the biosynthetic pathway of lincosamide antibiotics can bifurcate to generate different lincosamides, but also reveal the promiscuity of the enzymes involved.
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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
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g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳