A bacterial biosynthetic pathway for methylated furan fatty acids

Abstract

Fatty acids play many important roles in cells and also in industrial processes. Furan fatty acids (FuFAs) are present in the lipids of some plant, fish, and microbial species and appear to function as second messengers in pathways that protect cells from membrane-damaging agents. We report here the results of chemical, genetic, and synthetic biology experiments to decipher the biosynthesis of the monomethylated FuFA, methyl 9-(3-methyl-5-pentylfuran-2-yl) nonanoate (9M5-FuFA), and its dimethyl counterpart, methyl 9-(3,4-dimethyl-5-pentylfuran-2-yl) nonanoate (9D5-FuFA), in two α-proteobacteria. Each of the steps in FuFA biosynthesis occurs on pre-existing phospholipid fatty acid chains, and we identified pathway intermediates and the gene products that catalyze 9M5-FuFA and 9D5-FuFA synthesis in Rhodobacter sphaeroides 2.4.1 and Rhodopseudomonas palustris CGA009. One previously unknown pathway intermediate was a methylated diunsaturated fatty acid, (10E,12E)-11-methyloctadeca-10,12-dienoic acid (11Me-10t,12t-18:2), produced from (11E)-methyloctadeca-11-enoic acid (11Me-12t-18:1) by a newly identified fatty acid desaturase, UfaD. We also show that molecular oxygen (O2) is the source of the oxygen atom in the furan ring of 9M5-FuFA, and our findings predict that an O2-derived oxygen atom is incorporated into 9M5-FuFA via a protein, UfaO, that uses the 11Me-10t,12t-18:2 fatty acid phospholipid chain as a substrate. We discovered that R. palustris also contains a SAM-dependent methylase, FufM, that produces 9D5-FuFA from 9M5-FuFA. These results uncover the biochemical sequence of intermediates in a bacterial pathway for 9M5-FuFA and 9D5-FuFA biosynthesis and suggest the existence of homologs of the enzymes identified here that could function in FuFA biosynthesis in other organisms.

Enhanced Bioremediation Potential of Shewanella decolorationis RNA Polymerase Mutants and Evidence for Novel Azo Dye Biodegradation Pathways

“…Among them, two (i.e., D0436_05260 GS 0.78 and D0436_13105 GS 0.85) were anti-sigma factors positively correlated with AMR degradation. D0436_13105 encodes ChrR that has been identified as a σ 24 anti-factor ( Mauro et al, 2019 ; Lemke et al, 2020 ). One (i.e., D0436_03030 GS -0.92) was σ D (i.e., σ 70 ) a regulator that negatively correlated with AMR degradation.…”

Solving a furan fatty acid biosynthesis puzzle

“…In the current study, Lemke et al report elegant work defining the entire mono-and dimethyl FuFA biosynthesis pathway in photosynthetic bacteria (8). The authors had previously identified a R. sphaeroides mutant lacking the ChrR antisigma factor with increased abundance of FuFA, which served as a key to their success in dissecting the function of the RSP1087-1091 operon.…”

Furan Fatty Acids in Some 20 Fungi Species: Unique Profiles and Quantities

“…D-/M-FuFAs are biosynthesized by plants and bacteria, while humans and animals accumulate them from food and feed. ,, In bacteria, 9M5 and 9D5 were formed from (Z)-octadec-11-enoic acid (vaccenic acid), while linoleic acid has been suggested to be the precursor of FuFAs in plants . With a few exceptions, food from animals (e.g., fish, 30–900 mg/100 g fat and butter, 1.6–48 mg/100 g fat) ,, is richer in D-/M-FuFAs than most plant-derived samples [e.g., soy 14–65 mg/100 g fatty acid methyl esters (FAMEs), fresh spinach 0.07–6.6 mg/100 g fresh weight (FW), and herbs 0.2–2.2 mg/100 g FW]. ,− …”

“…11 In contrast to the complex IUPAC names [e.g., 9-(3,4-dimethyl-5-pentylfuran-2yl)-nonanoic acid], the shorthand names (here, 9D5) are simple to spell and use, and they provide full structural information, too (Figure 1). 11 D-/M-FuFAs are biosynthesized by plants 1 and bacteria, 12 while humans and animals accumulate them from food and feed. 1,8,13 In bacteria, 9M5 and 9D5 were formed from (Z)octadec-11-enoic acid (vaccenic acid), 2 while linoleic acid has been suggested to be the precursor of FuFAs in plants.…”