A Homologue of the Mycobacterium tuberculosis PapA5 Protein, Rif-Orf20, Is an Acetyltransferase Involved in the Biosynthesis of Antitubercular Drug Rifamycin B by Amycolatopsis mediterranei S699

ChemBioChem ◽  
2005 ◽  
Vol 6 (5) ◽  
pp. 834-837 ◽  
Author(s):  
Yeping Xiong ◽  
Xiumei Wu ◽  
Taifo Mahmud
2008 ◽  
Vol 53 (2) ◽  
pp. 808-810 ◽  
Author(s):  
Agustina I. de la Iglesia ◽  
Emma J. Stella ◽  
Héctor R. Morbidoni

ABSTRACT Resistance to rifampin (rifampicin), isoniazid, and streptomycin of 69 Mycobacterium tuberculosis isolates was analyzed by an in-house method based on mycobacteriophage D29 and a colorimetric micromethod. Both methods showed sensitivity and specificity values ranging from 93% to 100%. These simple methods offer an option for drug resistance assessment of M. tuberculosis.


1998 ◽  
Vol 51 (1) ◽  
pp. 58-63 ◽  
Author(s):  
ARMANDO MEJÍA ◽  
JAVIER BARRIOS-GONZÁLEZ ◽  
GUSTAVO VINIEGRA-GONZÁLEZ

2021 ◽  
Vol 19 (1) ◽  
pp. 1074-1088
Author(s):  
Olabisi Flora Davies-Bolorunduro ◽  
Abraham Ajayi ◽  
Isaac Adeyemi Adeleye ◽  
Alfinda Novi Kristanti ◽  
Nanik Siti Aminah

Abstract There has been an increase in the reported cases of tuberculosis, a disease caused by Mycobacterium tuberculosis, which is still currently affecting most of the world’s population, especially in resource-limited countries. The search for novel antitubercular chemotherapeutics from underexplored natural sources is therefore of paramount importance. The renewed interest in studies related to natural products, driven partly by the growing incidence of MDR-TB, has increased the prospects of discovering new antitubercular drug leads. This is because most of the currently available chemotherapeutics such as rifampicin and capreomycin used in the treatment of TB were derived from natural products, which are proven to be an abundant source of novel drugs used to treat many diseases. To meet the global need for novel antibiotics from natural sources, various strategies for high-throughput screening have been designed and implemented. This review highlights the current antitubercular drug discovery strategies from natural sources.


1999 ◽  
Vol 181 (4) ◽  
pp. 1343-1347 ◽  
Author(s):  
Mark Payton ◽  
Roy Auty ◽  
Rupika Delgoda ◽  
Martin Everett ◽  
Edith Sim

ABSTRACT Arylamine N-acetyltransferases (NATs) are found in many eukaryotic organisms, including humans, and have previously been identified in the prokaryote Salmonella typhimurium. NATs from many sources acetylate the antitubercular drug isoniazid and so inactivate it. nat genes were cloned fromMycobacterium smegmatis and Mycobacterium tuberculosis, and expressed in Escherichia coli andM. smegmatis. The induced M. smegmatis NAT catalyzes the acetylation of isoniazid. A monospecific antiserum raised against pure NAT from S. typhimurium recognizes NAT fromM. smegmatis and cross-reacts with recombinant NAT fromM. tuberculosis. Overexpression of mycobacterialnat genes in E. coli results in predominantly insoluble recombinant protein; however, with M. smegmatisas the host using the vector pACE-1, NAT proteins from M. tuberculosis and M. smegmatis are soluble. M. smegmatis transformants induced to express the M. tuberculosis nat gene in culture demonstrated a threefold higher resistance to isoniazid. We propose that NAT in mycobacteria could have a role in acetylating, and hence inactivating, isoniazid.


2008 ◽  
Vol 106 (5) ◽  
pp. 493-497 ◽  
Author(s):  
Guerra Priscila ◽  
Francisco J. Fernández ◽  
Angel E. Absalón ◽  
Ma. Del Rocío Suarez ◽  
Mara Sainoz ◽  
...  

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 920
Author(s):  
Yanrong Shi ◽  
Feng Ye ◽  
Yuliang Song ◽  
Xiaochun Zhang ◽  
Chunhua Lu ◽  
...  

Rifamycin W, the most predominant intermediate in the biosynthesis of rifamycin, needs to undergo polyketide backbone rearrangement to produce rifamycin B via an oxidative cleavage of the C-12/C-29 double bond. However, the mechanism of this putative oxidative cleavage has not been characterized yet. Rif-Orf5 (a putative cytochrome P450 monooxygenase) was proposed to be involved in the cleavage of this olefinic moiety of rifamycin W. In this study, the mutant strain Amycolatopsis mediterranei S699 Δrif-orf5 was constructed by in-frame deleting the rif-orf5 gene to afford thirteen rifamycin W congeners (1–13) including seven new ones (1–7). Their structures were elucidated by extensive analysis of 1D and 2D NMR spectroscopic data and high-resolution ESI mass spectra. Presumably, compounds 1–4 were derivatized from rifamycin W via C-5/C-11 retro-Claisen cleavage, and compounds 1–3, 9 and 10 featured a hemiacetal. Compounds 5–7 and 11 showed oxygenations at various sites of the ansa chain. In addition, compounds 1–3 exhibited antibacterial activity against Staphylococcus aureus with minimal inhibitory concentration (MIC) values of 5, 40 and 0.5 µg/mL, respectively. Compounds 1 and 3 showed modest antiproliferative activity against HeLa and Caco-2 cells with half maximal inhibitory concentration (IC50) values of about 50 µM.


Sign in / Sign up

Export Citation Format

Share Document