Fatty Acid Biosynthesis: an updated review on KAS inhibitors

2022 ◽  
Vol 19 ◽  
Author(s):  
Rani Shinde ◽  
Vasanti Suvarna
Keyword(s):  
Drug Resistance ◽  
Fatty Acid ◽  
Drug Targets ◽  
Fatty Acid Biosynthesis ◽  
Resistance Mechanisms ◽  
Acid Biosynthesis ◽  
E Coli ◽  
Metabolic Mechanism ◽  
Modern Era ◽  
Early Drug

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.

scholarly journals β-Ketoacyl-Acyl Carrier Protein Synthase III (FabH) Is a Determining Factor in Branched-Chain Fatty Acid Biosynthesis

2000 ◽  
Vol 182 (2) ◽  
pp. 365-370 ◽  
Author(s):  
Keum-Hwa Choi ◽  
Richard J. Heath ◽  
Charles O. Rock
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Fatty Acid Biosynthesis ◽  
Acyl Carrier Protein ◽  
Chain Fatty Acid ◽  
Carrier Protein ◽  
Acid Biosynthesis ◽  
Biochemical Basis ◽  
E Coli ◽  
Branched Chain

ABSTRACT A universal set of genes encodes the components of the dissociated, type II, fatty acid synthase system that is responsible for producing the multitude of fatty acid structures found in bacterial membranes. We examined the biochemical basis for the production of branched-chain fatty acids by gram-positive bacteria. Two genes that were predicted to encode homologs of the β-ketoacyl-acyl carrier protein synthase III of Escherichia coli (eFabH) were identified in theBacillus subtilis genome. Their protein products were expressed, purified, and biochemically characterized. Both B. subtilis FabH homologs, bFabH1 and bFabH2, carried out the initial condensation reaction of fatty acid biosynthesis with acetyl-coenzyme A (acetyl-CoA) as a primer, although they possessed lower specific activities than eFabH. bFabH1 and bFabH2 also utilized iso- and anteiso-branched-chain acyl-CoA primers as substrates. eFabH was not able to accept these CoA thioesters. Reconstitution of a complete round of fatty acid synthesis in vitro with purified E. coli proteins showed that eFabH was the only E. colienzyme incapable of using branched-chain substrates. Expression of either bFabH1 or bFabH2 in E. coli resulted in the appearance of a branched-chain 17-carbon fatty acid. Thus, the substrate specificity of FabH is an important determinant of branched-chain fatty acid production.

scholarly journals Elucidation of transient protein-protein interactions within carrier protein-dependent biosynthesis

2020 ◽  
Author(s):  
Michael Burkart ◽  
Thomas Bartholow ◽  
Terra Sztain ◽  
Ashay Patel ◽  
D Lee ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Protein Interactions ◽  
Fatty Acid Biosynthesis ◽  
De Novo ◽  
Acyl Carrier Protein ◽  
Protein Docking ◽  
Carrier Protein ◽  
Protein Protein Interactions ◽  
Acid Biosynthesis ◽  
E Coli

Abstract Fatty acid biosynthesis (FAB) is an essential and highly conserved metabolic pathway. In bacteria, this process is mediated by an elaborate network of protein•protein interactions (PPIs) involving a small, dynamic acyl carrier protein that interacts with dozens of other partner proteins (PPs). These PPIs have remained poorly characterized due to their dynamic and transient nature. Using a combination of solution-phase NMR spectroscopy and protein-protein docking simulations, we report a comprehensive residue-by-residue comparison of the PPIs formed during FAB in Escherichia coli. This work reveals the molecular basis of six discrete binding events responsible for E. coli FAB and offers insights into a method to characterize these events and those in related carrier protein-dependent pathways. ONE SENTENCE SUMMARY: Through a combination of structural and computational analysis, a comparative evaluation of protein-protein interactions in de novo fatty acid biosynthesis in E. coli is performed.

scholarly journals Engineering of E. coli inherent fatty acid biosynthesis capacity to increase octanoic acid production

2018 ◽  
Vol 11 (1) ◽  
Author(s):  
Zaigao Tan ◽  
Jong Moon Yoon ◽  
Anupam Chowdhury ◽  
Kaitlin Burdick ◽  
Laura R. Jarboe ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Acid Production ◽  
Octanoic Acid ◽  
Fatty Acid Biosynthesis ◽  
Acid Biosynthesis ◽  
E Coli

scholarly journals ‘FAS’t inhibition of malaria

2004 ◽  
Vol 383 (3) ◽  
pp. 401-412 ◽  
Author(s):  
Avadhesha SUROLIA ◽  
T. N. C. RAMYA ◽  
V. RAMYA ◽  
Namita SUROLIA
Keyword(s):  
Fatty Acid ◽  
Drug Targets ◽  
Fatty Acid Biosynthesis ◽  
Present Review ◽  
Acid Biosynthesis ◽  
The Status ◽  
Novel Drug ◽  
Emergence Of Resistance ◽  
Specific Pathway

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.

scholarly journals Elucidation of Protein-Protein Interactions Throughout E. coli Fatty Acid Biosynthesis

2020 ◽  
Vol 118 (3) ◽  
pp. 182a
Author(s):  
Thomas G. Bartholow ◽  
Terra Sztain-Pedone ◽  
Ashay Patel ◽  
Ruben Abagyan ◽  
Michael D. Burkart
Keyword(s):  
Fatty Acid ◽  
Protein Interactions ◽  
Fatty Acid Biosynthesis ◽  
Protein Protein Interactions ◽  
Acid Biosynthesis ◽  
E Coli

Quantitative analysis and engineering of fatty acid biosynthesis in E. coli

2010 ◽  
Vol 12 (4) ◽  
pp. 378-386 ◽  
Author(s):  
Tiangang Liu ◽  
Harmit Vora ◽  
Chaitan Khosla
Keyword(s):  
Fatty Acid ◽  
Quantitative Analysis ◽  
Fatty Acid Biosynthesis ◽  
Acid Biosynthesis ◽  
E Coli
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