Product‐Regulation Mechanisms for Fatty Acid Biosynthesis Catalyzed by <i>Mycobacterium smegmatis</i> FAS I

Παπαϊωάννου, Νικόλαος; Cheon, Hwan‐Sung; Lian, Yiqian; Kishi, Yoshito

doi:10.1002/cbic.200700380

Cited by 12 publications

(9 citation statements)

References 31 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Replacing the M. smegmatis FAS-I system with the Mtb homologue, did not alter the length of the longer fatty acid chains produced in M. smegmatis from the usual C 24 to the C 26 produced by Mtb; this indicates that regulation is not restricted to FAS-I and may involve interactions between FabH and FAS-II with FAS-I [125]. Endogenous polysaccharides also affect FAS-I product formation, favouring the synthesis of shorter chain fatty acids (C 16 -C 18 ) as well as increasing the overall rate of synthesis; these polysaccharides, containing 3-O-methyl-D-mannose or 6-O-methyl-D-glucose, are proposed to enhance product release, a rate-limiting step in the synthesis, by forming a complex specifically with the shorter length product and thereby facilitating its release [126][127][128]. In the absence of these polysaccharides, the synthesis of the longer fatty acid chain is favoured (C 24 -C 26 ), which as longer, shows an increased ability to self-interact, forming stable aggregates that also enable product release from FAS-I [126].…”

Section: Fatty Acid and Mycolic Acid Biosynthesismentioning

confidence: 99%

The thick waxy coat of mycobacteria, a protective layer against antibiotics and the host's immune system

Batt

Minnikin

Besra

2020

Biochemical Journal

110

131

View full text Add to dashboard Cite

Tuberculosis, caused by the pathogenic bacterium Mycobacterium tuberculosis (Mtb), is the leading cause of death from an infectious disease, with a mortality rate of over a million people per year. This pathogen's remarkable resilience and infectivity is largely due to its unique waxy cell envelope, 40% of which comprises complex lipids. Therefore, an understanding of the structure and function of the cell wall lipids is of huge indirect clinical significance. This review provides a synopsis of the cell envelope and the major lipids contained within, including structure, biosynthesis and roles in pathogenesis.

show abstract

Section: Fatty Acid and Mycolic Acid Biosynthesismentioning

confidence: 99%

The thick waxy coat of mycobacteria, a protective layer against antibiotics and the host's immune system

Batt

Minnikin

Besra

2020

Biochemical Journal

110

131

View full text Add to dashboard Cite

show abstract

“…For instance, early studies carried out with FAS I from M. smegmatis demonstrated that acyl‐CoA‐binding substances like bovine serum albumin or certain mycobacterial polysaccharides could shift the FAS product pattern of mycobacterial type I FAS toward shorter‐chain acids (Peterson & Bloch, 1977). More recently, Papaioannou et al (2007) studied the product‐regulation mechanisms for fatty acid biosynthesis catalyzed by M. smegmatis FAS I. They found that the predominant formation of palmitic acid in the presence of synthetic O ‐alkyl polysaccharide is regulated by the removal of the end‐product via a tight stoichiometric complex between the C 16:0 fatty acid and the O ‐alkyl polysaccharide (gate‐keeper mechanism) (Papaioannou et al , 2007).…”

Section: Fas Systems In Three Model Actinomycetesmentioning

confidence: 99%

“…More recently, Papaioannou et al (2007) studied the product‐regulation mechanisms for fatty acid biosynthesis catalyzed by M. smegmatis FAS I. They found that the predominant formation of palmitic acid in the presence of synthetic O ‐alkyl polysaccharide is regulated by the removal of the end‐product via a tight stoichiometric complex between the C 16:0 fatty acid and the O ‐alkyl polysaccharide (gate‐keeper mechanism) (Papaioannou et al , 2007). The bimodal pattern of product distribution has also been demonstrated with the yeast FAS, where the addition of acyl‐CoA‐binding protein to the assay mixture caused a dramatic decrease in the chain length of acyl‐CoA reaction products (Schjerling et al , 1996).…”

Section: Fas Systems In Three Model Actinomycetesmentioning

confidence: 99%

Fatty acid biosynthesis in actinomycetes

et al. 2011

View full text Add to dashboard Cite

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.

show abstract

“…The bimodal product distribution may also rely on intrinsic determinants of the FAS polypeptides and/or external factors affecting the elongation process. For example, studies on the product-regulation mechanisms for fatty acid biosynthesis catalyzed by M. smegmatis FAS I demonstrated that the formation of palmitic acid in the presence of synthetic O-alkyl polysaccharide is regulated by the removal of the end product via a tight stoichiometric complex between the C 16:0 fatty acid and the O-alkyl polysaccharide (63). In M. tuberculosis the C 26:0 fatty acids synthesized by FAS I, known as the α branch, will become the substrate of a dedicated acyl-CoA carboxylase to generate the α-carboxy C 26:0 fatty acid used as one of the substrates by the polyketide synthase Pks13.…”

Section: Fas I and Short-chain Fatty Acid Biosynthesismentioning

confidence: 99%

The Molecular Genetics of Mycolic Acid Biosynthesis

Pawełczyk

Kremer²

2014

Microbiol Spectr

View full text Add to dashboard Cite

Mycolic acids are major and specific long-chain fatty acids that represent essential components of the Mycobacterium tuberculosis cell envelope. They play a crucial role in the cell wall architecture and impermeability, hence the natural resistance of mycobacteria to most antibiotics, and represent key factors in mycobacterial virulence. Biosynthesis of mycolic acid precursors requires two types of fatty acid synthases (FASs), the eukaryotic-like multifunctional enzyme FAS I and the acyl carrier protein (ACP)-dependent FAS II systems, which consists of a series of discrete mono-functional proteins, each catalyzing one reaction in the pathway. Unlike FAS II synthases of other bacteria, the mycobacterial FAS II is incapable of de novo fatty acid synthesis from acetyl-coenzyme A, but instead elongates medium-chain-length fatty acids previously synthesized by FAS I, leading to meromycolic acids. In addition, mycolic acid subspecies with defined biological properties can be distinguished according to the chemical modifications decorating the meromycolate. Nearly all the genetic components involved in both elongation and functionalization of the meromycolic acid have been identified and are generally clustered in distinct transcriptional units. A large body of information has been generated on the enzymology of the mycolic acid biosynthetic pathway and on their genetic and biochemical/structural characterization as targets of several antitubercular drugs. This chapter is a comprehensive overview of mycolic acid structure, function, and biosynthesis. Special emphasis is given to recent work addressing the regulation of mycolic acid biosynthesis, adding new insights to our understanding of how pathogenic mycobacteria adapt their cell wall composition in response to environmental changes.

show abstract

Product‐Regulation Mechanisms for Fatty Acid Biosynthesis Catalyzed by Mycobacterium smegmatis FAS I

Cited by 12 publications

References 31 publications

The thick waxy coat of mycobacteria, a protective layer against antibiotics and the host's immune system

The thick waxy coat of mycobacteria, a protective layer against antibiotics and the host's immune system

Fatty acid biosynthesis in actinomycetes

The Molecular Genetics of Mycolic Acid Biosynthesis

Contact Info

Product

Resources

About