Collinone
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| Category | Antibiotics |
| Catalog number | BBF-01041 |
| CAS | 343315-22-0 |
| Molecular Weight | 534.42 |
| Molecular Formula | C27H18O12 |
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Description
It is produced by the strain of Streptomuces coelicolor CH999. It has anti-gram-positive bacterial activity including methicillin-resistant staphylococcus aureus (MRSA) and vancomycin resistant enterococcus (VRE). MIC is 16-32 μg/mL. It has no effect on gram-negative bacteria, fungi and viruses. It is toxic to HeLa, Vero, MT-4 and other tumor cells.
Specification
| IUPAC Name | (1S,14R)-1,3,14,15,26-pentahydroxy-21-methoxy-7-methyl-6-oxahexacyclo[12.12.0.02,11.04,9.016,25.018,23]hexacosa-2(11),3,7,9,15,18(23),20,25-octaene-5,17,19,22,24-pentone |
| Canonical SMILES | CC1=CC2=CC3=C(C(=C2C(=O)O1)O)C4(C(=C5C(=C(C4(CC3)O)O)C(=O)C6=C(C5=O)C(=O)C(=CC6=O)OC)O)O |
| InChI | InChI=1S/C27H18O12/c1-8-5-10-6-9-3-4-26(36)23(33)16-17(24(34)27(26,37)18(9)22(32)13(10)25(35)39-8)21(31)15-14(20(16)30)11(28)7-12(38-2)19(15)29/h5-7,32-34,36-37H,3-4H2,1-2H3/t26-,27+/m1/s1 |
| InChI Key | RIDFNHJMBSRPNA-SXOMAYOGSA-N |
Properties
| Appearance | Dark Red Solid |
| Antibiotic Activity Spectrum | Gram-positive bacteria; Neoplastics (Tumor) |
| Melting Point | 222-225 °C |
Reference Reading
1. Biosynthesis of pentangular polyphenols: deductions from the benastatin and griseorhodin pathways
Gerald Lackner, Angéla Schenk, Zhongli Xu, Kathrin Reinhardt, Zeynep S Yunt, Jörn Piel, Christian Hertweck J Am Chem Soc. 2007 Aug 1;129(30):9306-12. doi: 10.1021/ja0718624. Epub 2007 Jul 11.
The benastatins, pradimicins, fredericamycins, and members of the griseorhodin/rubromycin family represent a structurally and functionally diverse group of long-chain polyphenols from actinomycetes. Comparison of their biosynthetic gene clusters (ben, prm, fdm, grh, rub) revealed that all loci harbor genes coding for a similar, yet uncharacterized, type of ketoreductases. In a phylogenetic survey of representative KRs involved in type II PKS systems, we found that it is generally possible to deduce the KR regiospecificity (C-9, C-15, C17) from the amino acid sequence and thus to predict the nature of the aromatic polyketide (e.g., angucycline, anthracycline, benzoisochromanequinones). We hypothezised that the new clade of KRs is characteristic for biosynthesis of polyphenols with an extended angular architecture we termed "pentangular". To test this hypothesis, we demonstrated the biogenetic relationship between benastatin and the structurally unrelated spiro ketal griseorhodin by generating a mutant producing collinone, a pentangular pathway intermediate. The benastatin pathway served as a model to characterize the KR. Gene inactivation of benL resulted in the formation of a series of 19-hydroxy benastatin and bequinostatin derivatives (e.g., benastatin K and benastatin L). These results clearly showed that BenL functions as a C-19 KR in pentangular pathways.
2. Catalytic Control of Spiroketal Formation in Rubromycin Polyketide Biosynthesis
Marina Toplak, Raspudin Saleem-Batcha, Jörn Piel, Robin Teufel Angew Chem Int Ed Engl. 2021 Dec 20;60(52):26960-26970. doi: 10.1002/anie.202109384. Epub 2021 Nov 10.
The medically important bacterial aromatic polyketide natural products typically feature a planar, polycyclic core structure. An exception is found for the rubromycins, whose backbones are disrupted by a bisbenzannulated [5,6]-spiroketal pharmacophore that was recently shown to be assembled by flavin-dependent enzymes. In particular, a flavoprotein monooxygenase proved critical for the drastic oxidative rearrangement of a pentangular precursor and the installment of an intermediate [6,6]-spiroketal moiety. Here we provide structural and mechanistic insights into the control of catalysis by this spiroketal synthase, which fulfills several important functions as reductase, monooxygenase, and presumably oxidase. The enzyme hereby tightly controls the redox state of the substrate to counteract shunt product formation, while also steering the cleavage of three carbon-carbon bonds. Our work illustrates an exceptional strategy for the biosynthesis of stable chroman spiroketals.
3. An acetyltransferase controls the metabolic flux in rubromycin polyketide biosynthesis by direct modulation of redox tailoring enzymes
Marina Toplak, Adelheid Nagel, Britta Frensch, Thorsten Lechtenberg, Robin Teufel Chem Sci. 2022 May 17;13(24):7157-7164. doi: 10.1039/d2sc01952c. eCollection 2022 Jun 22.
The often complex control of bacterial natural product biosynthesis typically involves global and pathway-specific transcriptional regulators of gene expression, which often limits the yield of bioactive compounds under laboratory conditions. However, little is known about regulation mechanisms on the enzymatic level. Here, we report a novel regulatory principle for natural products involving a dedicated acetyltransferase, which modifies a redox-tailoring enzyme and thereby enables pathway furcation and alternating pharmacophore assembly in rubromycin polyketide biosynthesis. The rubromycins such as griseorhodin (grh) A are complex bioactive aromatic polyketides from Actinobacteria with a hallmark bisbenzannulated [5,6]-spiroketal pharmacophore that is mainly installed by two flavoprotein monooxygenases. First, GrhO5 converts the advanced precursor collinone into the [6,6]-spiroketal containing dihydrolenticulone, before GrhO6 effectuates a ring contraction to afford the [5,6]-spiroketal. Our results show that pharmacophore assembly in addition involves the acetyl-CoA-dependent acetyltransferase GrhJ that activates GrhO6 to allow the rapid generation and release of its labile product, which is subsequently sequestered by ketoreductase GrhO10 and converted into a stable intermediate. Consequently, the biosynthesis is directed to the generation of canonical rubromycins, while the alternative spontaneous [5,6]-spiroketal hydrolysis to a ring-opened pathway product is thwarted. Presumably, this allows the bacteria to rapidly adjust the biosynthesis of functionally distinct secondary metabolites depending on nutrient and precursor (i.e. acetyl-CoA) availability. Our study thus illustrates how natural product biosynthesis can be enzymatically regulated and provides new perspectives for the improvement of in vitro enzyme activities and natural product titers via biotechnological approaches.
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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 ╳
