scholarly journals Cofactors in Fatty Acid Biosynthesis—Active Site Organizers and Drug Targets

Structure ◽  
2004 ◽  
Vol 12 (3) ◽  
pp. 358-359 ◽  
Author(s):  
H.Tonie Wright
2004 ◽  
Vol 383 (3) ◽  
pp. 401-412 ◽  
Author(s):  
Avadhesha SUROLIA ◽  
T. N. C. RAMYA ◽  
V. RAMYA ◽  
Namita SUROLIA

Malaria, a tropical disease caused by Plasmodium sp., has been haunting mankind for ages. Unsuccessful attempts to develop a vaccine, the emergence of resistance against the existing drugs and the increasing mortality rate all call for immediate strategies to treat it. Intense attempts are underway to develop potent analogues of the current antimalarials, as well as a search for novel drug targets in the parasite. The indispensability of apicoplast (plastid) to the survival of the parasite has attracted a lot of attention in the recent past. The present review describes the origin and the essentiality of this relict organelle to the parasite. We also show that among the apicoplast specific pathways, the fatty acid biosynthesis system is an attractive target, because its inhibition decimates the parasite swiftly unlike the ‘delayed death’ phenotype exhibited by the inhibition of the other apicoplast processes. As the enzymes of the fatty acid biosynthesis system are present as discrete entities, unlike those of the host, they are amenable to inhibition without impairing the operation of the host-specific pathway. The present review describes the role of these enzymes, the status of their molecular characterization and the current advancements in the area of developing inhibitors against each of the enzymes of the pathway.


Author(s):  
Rani Shinde ◽  
Vasanti Suvarna

Abstract: Since the early twentieth century, with the isolation of penicillin and streptomycin in the 1940s, the modern era of anti-infective drug development has gained momentum. Due to the enormous success of early drug discovery, many infectious diseases were successfully prevented & eradicated. However, this initial hope was wrongheaded, and pathogens evolved as a significant threat to human health. Drug resistance develops as a result of natural selection's relentless pressure, necessitating the identification of new drug targets and the creation of chemotherapeutics that bypass existing drug resistance mechanisms. Fatty acid biosynthesis (FAS) is a crucial metabolic mechanism for bacteria during their growth and development. Several crucial enzymes involved in this biosynthetic pathway have been identified as potential targets for new antibacterial agents. In Escherichia coli (E. coli), this pathway has been extensively investigated. The present review focuses on progress in the development of Kas A, Kas B, and Fab H inhibitors as mono-therapeutic antibiotics.


1991 ◽  
Vol 81 (2) ◽  
pp. 251-255
Author(s):  
Manfred Focke ◽  
Andrea Feld ◽  
Hartmut K. Lichtenthaler

Author(s):  
L. K. Dahiwade ◽  
S. R. Rochlani ◽  
P. B. Choudhari ◽  
R. P. Dhavale ◽  
H. N. Moreira

Background: Mycobacterium tuberculosis is a causative organism of tuberculosis, which is most deadly disease after cancer in a current decade. The development of multidrug and broadly drug- resistant strains making the tuberculosis problem more and more critical. In last 40 years, only one molecule is added to the treatment regimen. Generally, drug design and development programs are targeted proteins whose function is known to be essential to the bacterial cell. Objectives: Reported here are the development of 'S', 'N’ heterocycles as antimycobacterials targeting fatty acid biosynthesis. Material and Methods: In the present communication, rational development of anti-mycobacterial agent's targeting fatty acid biosynthesis has been done by integrating the pocket modelling and virtual analysis. Results: The identified potential 33 lead compounds were synthesized, characterized by physicochemical and spectroscopic methods like IR, NMR spectroscopy and further screened for antimycobacterial activity using isoniazid as standard. All the designed compounds have shown profound antimycobacterial activity. Conclusion: In this present communication, we found that 3c, 3f, 3l and 4k molecules had expressive desirable biological activity and specific interactions with fatty acids. Further optimization of these leads is necessary for the development of potential antimycobacterial drug candidate having less side effects.


Plants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 706
Author(s):  
Antonio J. Moreno-Pérez ◽  
Raquel Martins-Noguerol ◽  
Cristina DeAndrés-Gil ◽  
Mónica Venegas-Calerón ◽  
Rosario Sánchez ◽  
...  

Histone modifications are of paramount importance during plant development. Investigating chromatin remodeling in developing oilseeds sheds light on the molecular mechanisms controlling fatty acid metabolism and facilitates the identification of new functional regions in oil crop genomes. The present study characterizes the epigenetic modifications H3K4me3 in relationship with the expression of fatty acid-related genes and transcription factors in developing sunflower seeds. Two master transcriptional regulators identified in this analysis, VIV1 (homologous to Arabidopsis ABI3) and FUS3, cooperate in the regulation of WRINKLED 1, a transcriptional factor regulating glycolysis, and fatty acid synthesis in developing oilseeds.


2021 ◽  
Vol 22 (11) ◽  
pp. 5951
Author(s):  
Xiaofei Zhou ◽  
Xiaoyu Ling ◽  
Huijuan Guo ◽  
Keyan Zhu-Salzman ◽  
Feng Ge ◽  
...  

Bacterial symbionts associated with insects are often involved in host development and ecological adaptation. Serratia symbiotica, a common facultative endosymbiont harbored in pea aphids, improves host fitness and heat tolerance, but studies concerning the nutritional metabolism and impact on the aphid host associated with carrying Serratia are limited. In the current study, we showed that Serratia-infected aphids had a shorter nymphal developmental time and higher body weight than Serratia-free aphids when fed on detached leaves. Genes connecting to fatty acid biosynthesis and elongation were up-regulated in Serratia-infected aphids. Specifically, elevated expression of fatty acid synthase 1 (FASN1) and diacylglycerol-o-acyltransferase 2 (DGAT2) could result in accumulation of myristic acid, palmitic acid, linoleic acid, and arachidic acid in fat bodies. Impairing fatty acid synthesis in Serratia-infected pea aphids either by a pharmacological inhibitor or through silencing FASN1 and DGAT2 expression prolonged the nymphal growth period and decreased the aphid body weight. Conversely, supplementation of myristic acid (C14:0) to these aphids restored their normal development and weight gain. Our results indicated that Serratia promoted development and growth of its aphid host through enhancing fatty acid biosynthesis. Our discovery has shed more light on nutritional effects underlying the symbiosis between aphids and facultative endosymbionts.


1973 ◽  
Vol 248 (4) ◽  
pp. 1268-1276 ◽  
Author(s):  
Richard A. Jacobs ◽  
William S. Sly ◽  
Philip W. Majerus

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