Fatty acid biosynthesis in actinomycetes

Abstract

All organisms that produce fatty acids do so via a repeated cycle of reactions. In mammals and other animals, these reactions are catalyzed by a type I fatty acid synthase (FAS), a large multifunctional protein to which the growing chain is covalently attached. In contrast, most bacteria (and plants) contain a type II system in which each reaction is catalyzed by a discrete protein. The pathway of fatty acid biosynthesis in Escherichia coli is well established and has provided a foundation for elucidating the type II FAS pathways in other bacteria (White et al., 2005). However, fatty acid biosynthesis is more diverse in the phylum Actinobacteria: Mycobacterium, possess both FAS systems while Streptomyces species have only the multi-enzyme FAS II system and Corynebacterium species exclusively FAS I. In this review we present an overview of the genome organization, biochemical properties and physiological relevance of the two FAS systems in the three genera of actinomycetes mentioned above. We also address in detail the biochemical and structural properties of the acyl-CoA carboxylases (ACCases) that catalyzes the first committed step of fatty acid synthesis in actinomycetes, and discuss the molecular bases of their substrate specificity and the structure-based identification of new ACCase inhibitors with anti-mycobacterial properties.

Pseudomonas aeruginosa Directly Shunts β-Oxidation Degradation Intermediates into De Novo Fatty Acid Biosynthesis

“…S3E in the supplemental material). In E. coli, odd-numbered fatty acids arise though utilization of propionyl primers as alternative substrates to acetyl-CoA for FAS by FabH (23,27). The low-abundance d 7 -C 16:0 peak that is present only in perdeuterated C 10 -fed E. coli wild-type or TMY32 [fabH::catR(pET-FabY)] may arise through utilization of d 7 -butyryl-CoA produced by the ␤-oxidation cycle as a FAS primer by either FabH or FabY, respectively.…”

De novo assembly and analysis of Cassia obtusifolia seed transcriptome to identify genes involved in the biosynthesis of active metabolites

“…1 in C. obtusifolia. Under the molecular function category, binding (15,016,42.95%) represented the most abundant term, followed by catalytic activity (14,067, 40.24%) and transporter activity (2024, 4.98%). About 19,424 unigenes were annotated as "metabolic process" category, suggesting this study may allow for the identification of novel genes involved in the secondary metabolite synthesis pathways.…”

“…This reaction is catalyzed by acetyl-CoA carboxylase (ACCase). The ACCase gene was cloned and characterized from bacteria, animals, and plants 15,16) showed that the over-expressed ACCase gene could increase the content of lipid. Therefore, it was suggested that the ACCase catalyzes a rate-limiting step of the lipid biosynthesis pathway.…”

Biotin biosynthesis in Mycobacterium tuberculosis: physiology, biochemistry and molecular intervention

“…In contrast, ACC has been the subject of greater research focus primarily due to its potential as an antibiotic drug target (Wright and Reynolds, 2007;Chan and Vogel, 2010;Parsons and Rock, 2011). ACC catalyses the carboxylation of various acyl CoA substrates, such as acetyl CoA, propionyl CoA and butyryl CoA (Arabolaza et al, 2010;Gago et al, 2011). The products of these reactions feed into the fatty acid synthesis and polyketide synthesis pathways, resulting in the production of mycolic acids and multimethyl-branched fatty acids present in the cell envelope (Takayama et al, 2005;Gago et al, 2011).…”

“…ACC catalyses the carboxylation of various acyl CoA substrates, such as acetyl CoA, propionyl CoA and butyryl CoA (Arabolaza et al, 2010;Gago et al, 2011). The products of these reactions feed into the fatty acid synthesis and polyketide synthesis pathways, resulting in the production of mycolic acids and multimethyl-branched fatty acids present in the cell envelope (Takayama et al, 2005;Gago et al, 2011). These pathways are especially important in Mycobacterium sp., as the cell envelope contains a complex lipid bi-layer composed primarily of mycolic acid.…”