A short-chain acyl-CoA synthetase that supports branched-chain fatty acid synthesis in Staphylococcus aureus

Whaley, Sarah G.; Frank, Matthew W.; Rock, Charles O.

doi:10.1016/j.jbc.2023.103036

Cited by 10 publications

(13 citation statements)

References 48 publications

(77 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We present genetic and biochemical evidence that the gene product we now call MbcS is a member of the AMP‐forming acyl‐CoA synthetases and catalyzes the activation of BCCAs to their acyl‐CoAs with a preference for i C 4 and a C 5 substrates. Is important to note that, while this work was in preparation, the role of MbcS in BCFA synthesis was independently reported by Whaley et al., 2023. Furthermore, we show that the branched‐chain aldehyde 2‐methylbutyraldehyde and secreted products from S. epidermidis can also restore BCFA synthesis in the lpdA mutant, revealing the existence of an alternative route to BCFA synthesis.…”

Section: Introductionsupporting

confidence: 74%

“…Given their critical roles, it is difficult to imagine that there is no redundancy in the pathways that lead to their synthesis. On the other hand, disrupt- is required for salvaging exogenous carboxylic acids and aldehydes for BCFA synthesis when the BKDH complex is inactivated ( (Sen et al, 2016;Whaley et al, 2023). Interestingly, BCFA auxotrophy is resolved in our suppressor mutants by incorporating i14:0 BCFA into membranes derived from iC 4 (Figure 3).…”

Section: Discussionmentioning

confidence: 96%

“…Interestingly, BCFA auxotrophy is resolved in our suppressor mutants by incorporating i14:0 BCFA into membranes derived from iC 4 (Figure 3). This makes physiological sense -while FabH prefers aC 5 -CoA to initiate fatty acid synthesis, incorporating iso even fatty acids into the bilayer reflects not only the affinity of MbcS for substrate, but also the availability of the acyl-CoA precursor pool and the exogenous carboxylic acids from which they are formed (Whaley et al, 2023). Finally, we note that in contrast to the Whaley et al study where they report a ~5fold increase in affinity for aC 5 over iC 4 , we did not measure a significant difference in MbcS affinity for iC 4 or aC 5 .…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

In Staphylococcus aureus, the acyl‐CoA synthetase MbcS supports branched‐chain fatty acid synthesis from carboxylic acid and aldehyde precursors

dos Santos Ferreira,

Pendleton,

Yeo

et al. 2024

Molecular Microbiology

View full text Add to dashboard Cite

In the human pathogen Staphylococcus aureus, branched‐chain fatty acids (BCFAs) are the most abundant fatty acids in membrane phospholipids. Strains deficient for BCFAs synthesis experience auxotrophy in laboratory culture and attenuated virulence during infection. Furthermore, the membrane of S. aureus is among the main targets for antibiotic therapy. Therefore, determining the mechanisms involved in BCFAs synthesis is critical to manage S. aureus infections. Here, we report that the overexpression of SAUSA300_2542 (annotated to encode an acyl‐CoA synthetase) restores BCFAs synthesis in strains lacking the canonical biosynthetic pathway catalyzed by the branched‐chain α‐keto acid dehydrogenase (BKDH) complex. We demonstrate that the acyl‐CoA synthetase activity of MbcS activates branched‐chain carboxylic acids (BCCAs), and is required by S. aureus to utilize the isoleucine derivative 2‐methylbutyraldehyde to restore BCFAs synthesis in S. aureus. Based on the ability of some staphylococci to convert branched‐chain aldehydes into their respective BCCAs and our findings demonstrating that branched‐chain aldehydes are in fact BCFAs precursors, we propose that MbcS promotes the scavenging of exogenous BCCAs and mediates BCFA synthesis via a de novo alternative pathway.

show abstract

Section: Introductionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

In Staphylococcus aureus, the acyl‐CoA synthetase MbcS supports branched‐chain fatty acid synthesis from carboxylic acid and aldehyde precursors

dos Santos Ferreira,

Pendleton,

Yeo

et al. 2024

Molecular Microbiology

View full text Add to dashboard Cite

show abstract

“…These α-ketoacids are converted to branched-chain acyl-CoAs by Bkd. These acyl-CoAs are employed by 3-ketoacyl-ACP synthase III (FabH) to activate the bacterial fatty acid biosynthesis cycle to form BCFAs (Figure c) …”

Section: Gut Metabolitescfamentioning

confidence: 99%

“…These acyl-CoAs are employed by 3-ketoacyl-ACP synthase III (FabH) to activate the bacterial fatty acid biosynthesis cycle to form BCFAs (Figure 2c). 48 2.4. Cross-Feeding Mechanisms.…”

Section: Catabolism Of Amino Acids For Scfas and Bcfasmentioning

confidence: 99%

Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis─A Potential Therapeutic Intervention to Improve Lung Health

Verma,

Bhagchandani,

Rai

et al. 2024

ACS Omega

View full text Add to dashboard Cite

The microbiome is an integral part of the human gut, and it plays a crucial role in the development of the immune system and homeostasis. Apart from the gut microbiome, the airway microbial community also forms a distinct and crucial part of the human microbiota. Furthermore, several studies indicate the existence of communication between the gut microbiome and their metabolites with the lung airways, called "gut−lung axis". Perturbations in gut microbiota composition, termed dysbiosis, can have acute and chronic effects on the pathophysiology of lung diseases. Microbes and their metabolites in lung stimulate various innate immune pathways, which modulate the expression of the inflammatory genes in pulmonary leukocytes. For instance, gut microbiota-derived metabolites such as short-chain fatty acids can suppress lung inflammation through the activation of G protein-coupled receptors (free fatty acid receptors) and can also inhibit histone deacetylase, which in turn influences the severity of acute and chronic respiratory diseases. Thus, modulation of the gut microbiome composition through probiotic/prebiotic usage and fecal microbiota transplantation can lead to alterations in lung homeostasis and immunity. The resulting manipulation of immune cells function through microbiota and their key metabolites paves the way for the development of novel therapeutic strategies in improving the lung health of individuals affected with various lung diseases including SARS-CoV-2. This review will shed light upon the mechanistic aspect of immune system programming through gut and lung microbiota and exploration of the relationship between gut−lung microbiome and also highlight the therapeutic potential of gut microbiota-derived metabolites in the management of respiratory diseases.

show abstract

Elevated levels of branched chain fatty acids in low‐salt fish sauce by co‐fermentation: flavor improvement and metabolism analysis

Zhou,

Wu,

Monto

et al. 2024

J Sci Food Agric

View full text Add to dashboard Cite

BACKGROUNDTraditional fish sauce products rely on relatively long fermentation time and high salt concentration, resulting in inconsistent quality and health risks. Branched‐chain fatty acids (BCFAs) are associated with nutritional benefits and health‐care effects, mainly derived from food fermentation. This study aimed to screen BCFAs‐producing bacteria with high protease and aminotransferase activity as starter cultures for fish sauce fermentation.RESULTSThe low‐salt fish sauce products were obtained by co‐fermentation with three chosen strains. Trichloroacetic acid (TCA)‐soluble peptides and amino acid nitrogen concentrations were higher in the co‐fermentation group (FH group). The organoleptic evaluation showed co‐fermentation optimized flavor composition and endured with rich taste. The levels of BCFAs and branched‐chain amino acids (BCAAs) significantly increased by co‐fermentation. Volatile metabolomics analysis indicated that BCFAs, branched‐chain esters, and pyrazines were the key flavor compounds in the co‐fermented group.CONCLUSIONThe co‐fermentation system with selected strains to ferment low‐salt fish sauce has the potential to increase BCFA content and improve flavor and nutrition. © 2024 Society of Chemical Industry.

show abstract

A short-chain acyl-CoA synthetase that supports branched-chain fatty acid synthesis in Staphylococcus aureus

Cited by 10 publications

References 48 publications

In Staphylococcus aureus, the acyl‐CoA synthetase MbcS supports branched‐chain fatty acid synthesis from carboxylic acid and aldehyde precursors

In Staphylococcus aureus, the acyl‐CoA synthetase MbcS supports branched‐chain fatty acid synthesis from carboxylic acid and aldehyde precursors

Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis─A Potential Therapeutic Intervention to Improve Lung Health

Elevated levels of branched chain fatty acids in low‐salt fish sauce by co‐fermentation: flavor improvement and metabolism analysis

Contact Info

Product

Resources

About