Microbial Production of Conjugated Linoleic Acid and Conjugated Linolenic Acid Relies on a Multienzymatic System

Abstract

Conjugated linoleic acids (CLAs) and conjugated linolenic acids (CLNAs) have gained significant attention due to their anticarcinogenic and lipid/energy metabolism-modulatory effects. However, their concentration in foodstuffs is insufficient for any therapeutic application to be implemented. From a biotechnological standpoint, microbial production of these conjugated fatty acids (CFAs) has been explored as an alternative, and strains of the genera ,, and have shown promising producing capacities. Current screening research works are generally based on direct analytical determination of production capacity (e.g., trial and error), representing an important bottleneck in these studies. This review aims to summarize the available information regarding identified genes and proteins involved in CLA/CLNA production by these groups of bacteria and, consequently, the possible enzymatic reactions behind such metabolic processes. Linoleate isomerase (LAI) was the first enzyme to be described to be involved in the microbiological transformation of linoleic acids (LAs) and linolenic acids (LNAs) into CFA isomers. Thus, the availability of gene sequences has allowed the development of genetic screening tools. Nevertheless, several studies have reported that LAIs have significant homology with myosin-cross-reactive antigen (MCRA) proteins, which are involved in the synthesis of hydroxy fatty acids, as shown by hydratase activity. Furthermore, it has been suggested that CLA and/or CLNA production results from a stress response performed by the activation of more than one gene in a multiple-step reaction. Studies on CFA biochemical pathways are essential to understand and characterize the metabolic mechanism behind this process, unraveling all the gene products that may be involved. As some of these bacteria have shown modulation of lipid metabolism , further research to be focused on this topic may help us to understand the role of the gut microbiota in human health.

Effect of Pufa Substrates on Fatty Acid Profile of Bifidobacterium breve Ncimb 702258 and CLA/CLNA Production in Commercial Semi-Skimmed Milk

“…Fatty acid synthesis by microorganisms plays an important role in their adaptation to stress and proliferation such that inhibition of this pathway is currently been assayed as alternative solutions to control pathogenic strains 20 , 21 . Interestingly, unsaturated fatty acids and mainly LA, have been proven to alter the activity of bacterial enzymes involved in the elongation limiting-steps 22 in agreement with investigations suggesting that CFA production is a detoxifying mechanism 23 , 24 . Accordingly, this research work raises the hypothesis that inhibition by these FA is associated with alteration of membrane lipids profile, possibly changes in the levels of palmitic or stearic acids.…”

Linoleic acid induces metabolic stress in the intestinal microorganism Bifidobacterium breve DSM 20213

“…Regarding FA, we also highlighted an up-accumulation trend for some hydroxy-and oxo-fatty acids, such as 18-oxo-oleate (LogFC = 19.0 and 2.0 at the lag and exponential phase, respectively), 18-hydroxy-oleate (LogFC = 22.0 and 3.0 at the lag and exponential phase, respectively) and 18-hydroxy-stearate (LogFC = 19.0 and 1.0 at the lag and exponential phase, respectively and 16-hydroxy-15-methyl-palmitate (LogFC = 17.8) were also accumulated. Consistently, gut microbiota has been reported to produce hydroxy-and oxo-FAs from LA 28 . Additionally, Fernández-Murga and colleagues 29 noticed in Lactobacillus acidophilus an increase in hydroxyl-fatty acids when this bacterium grows at suboptimal temperatures.…”

A Solution to Antifolate Resistance in Group B Streptococcus : Untargeted Metabolomics Identifies Human Milk Oligosaccharide-Induced Perturbations That Result in Potentiation of Trimethoprim

“…Linoleic acid metabolites play a critical role in both cellular signaling and the stress response. Each is also critical to proper membrane construction (60,61). All identified linoleic acid metabolites were accumulated in the HMO-treated population, with several metabolites having a Ͼ100-fold increase from the untreated controls (Fig.…”