Probing fatty acid metabolism in bacteria, cyanobacteria, green microalgae and diatoms with natural and unnatural fatty acids

Beld, Joris; Abbriano, Raffaela M.; Finzel, Kara; Hildebrand, Mark; Burkart, Michael D.

doi:10.1039/c5mb00804b

Cited by 25 publications

(29 citation statements)

References 81 publications

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“…Primary role of fatty acids is to act as the hydrophobic component of the membrane lipids in both eukaryotes and prokaryotes [ 33 ]. Fatty acid synthases are responsible for the biosynthesis of fatty acids, extending its length by two carbon units every cycle [ 41 ]. Meanwhile, some of the intermediate metabolites are important precursors for synthesis of many bioproducts [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

Re-direction of carbon flux to key precursor malonyl-CoA via artificial small RNAs in photosynthetic Synechocystis sp. PCC 6803

Sun

Song

et al. 2018

Biotechnol Biofuels

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BackgroundPhotosynthetic cyanobacteria have attracted a significant attention as promising chassis to produce renewable fuels and chemicals due to their capability to utilizing solar energy and CO2. Notably, the enhancing supply of key precursors like malonyl-CoA would benefit the production of many bio-compounds. Nevertheless, the lacking of genetic tools in cyanobacteria, especially the knockdown strategies for essential pathways, has seriously restricted the attempts to re-direct carbon flux from the central carbohydrate metabolism to the synthesis of bioproducts.ResultsAiming at developing new genetic tools, two small RNA regulatory tools are reported for the model cyanobacterium Synechocystis sp. PCC6803, based on paired termini RNAs as well as the exogenous Hfq chaperone and MicC scaffold (Hfq-MicC) previously developed in Escherichia coli. Both regulatory tools functioned well in regulating exogenous reporter gene lacZ and endogenous glgC gene in Synechocystis sp. PCC6803, achieving a downregulation of gene expression up to 90% compared with wildtype. In addition, the Hfq-MicC tool was developed to simultaneously regulate multiple genes related to essential fatty acids biosynthesis, which led to decreased fatty acids content by 11%. Furthermore, aiming to re-direct the carbon flux, the Hfq-MicC tool was utilized to interfere the competing pathway of malonyl-CoA, achieving an increased intracellular malonyl-CoA abundance up to 41% (~ 698.3 pg/mL/OD730 nm) compared to the wildtype. Finally, the Hfq-MicC system was further modified into an inducible system based on the theophylline-inducible riboswitch.ConclusionsIn this study, two small RNA regulatory tools for manipulating essential metabolic pathways and re-directing carbon flux are reported for Synechocystis sp. PCC6803. The work introduces efficient and valuable metabolic regulatory strategies for photosynthetic cyanobacteria.Electronic supplementary materialThe online version of this article (10.1186/s13068-018-1032-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Re-direction of carbon flux to key precursor malonyl-CoA via artificial small RNAs in photosynthetic Synechocystis sp. PCC 6803

Sun

Song

et al. 2018

Biotechnol Biofuels

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“…The Synechocystis genome encodes no proteins with homology to enzymes involved in β-oxidation (Supplementary Table S2), although one report has suggested that the capacity for fatty acid catabolism is retained [138]. If so, there must be an alternate, uncharacterized pathway responsible for lipid degradation.…”

Section: Lipid Biosynthesismentioning

confidence: 99%

Current knowledge and recent advances in understanding metabolism of the model cyanobacteriumSynechocystissp. PCC 6803

2020

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Cyanobacteria are key organisms in the global ecosystem, useful models for studying metabolic and physiological processes conserved in photosynthetic organisms, and potential renewable platforms for production of chemicals. Characterizing cyanobacterial metabolism and physiology is key to understanding their role in the environment and unlocking their potential for biotechnology applications. Many aspects of cyanobacterial biology differ from heterotrophic bacteria. For example, most cyanobacteria incorporate a series of internal thylakoid membranes where both oxygenic photosynthesis and respiration occur, while CO2 fixation takes place in specialized compartments termed carboxysomes. In this review, we provide a comprehensive summary of our knowledge on cyanobacterial physiology and the pathways in Synechocystis sp. PCC 6803 (Synechocystis) involved in biosynthesis of sugar-based metabolites, amino acids, nucleotides, lipids, cofactors, vitamins, isoprenoids, pigments and cell wall components, in addition to the proteins involved in metabolite transport. While some pathways are conserved between model cyanobacteria, such as Synechocystis, and model heterotrophic bacteria like Escherichia coli, many enzymes and/or pathways involved in the biosynthesis of key metabolites in cyanobacteria have not been completely characterized. These include pathways required for biosynthesis of chorismate and membrane lipids, nucleotides, several amino acids, vitamins and cofactors, and isoprenoids such as plastoquinone, carotenoids, and tocopherols. Moreover, our understanding of photorespiration, lipopolysaccharide assembly and transport, and degradation of lipids, sucrose, most vitamins and amino acids, and haem, is incomplete. We discuss tools that may aid our understanding of cyanobacterial metabolism, notably CyanoSource, a barcoded library of targeted Synechocystis mutants, which will significantly accelerate characterization of individual proteins.

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“…We envisioned that an apparent inability of cyanobacteria to carry out canonical beta-oxidation of FAs coupled to the capacity to elongate exogenously-supplied FAs 31,32 would allow for extensive labeling of their FA-derived lipidome ( Fig. 1a) using stable-isotope labeled-precursors (as observed by Burkart et al 31 in Synechocystis sp. PCC 6803).…”

Section: Ms-guided Isolationmentioning

confidence: 99%

Discovery of Cyanobacterial Natural Products Containing Fatty Acid Residues

Figueiredo¹,

Preto²,

Moreira³

et al. 2020

Preprint

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Natural products have an important role in several human activities, most notably as sources of new drugs. In recent years, massive sequencing and annotation of bacterial genomes has revealed an unexpectedly large number of secondary metabolite biosynthetic gene clusters whose products are yet to be discovered. For example, cyanobacterial genomes contain a large number of gene clusters that likely incorporate fatty acid-derived moieties, but for most cases we lack the knowledge and tools to effectively predict or detect the encoded natural products. Here, we exploit the apparent lack of a functional beta-oxidation pathway in cyanobacteria to achieve efficient stable-isotope labeling of their fatty acid-derived lipidome. We show that supplementation of cyanobacterial cultures with deuterated fatty acids can be used to easily detect natural product signatures in individual strains. The utility of this strategy is demonstrated in two cultured cyanobacteria by uncovering analogues of the multidrug-resistance reverting hapalosin, and novel, cytotoxic, lactylate-nocuolin A hybrids – the nocuolactylates.

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Probing fatty acid metabolism in bacteria, cyanobacteria, green microalgae and diatoms with natural and unnatural fatty acids

Cited by 25 publications

References 81 publications

Re-direction of carbon flux to key precursor malonyl-CoA via artificial small RNAs in photosynthetic Synechocystis sp. PCC 6803

Re-direction of carbon flux to key precursor malonyl-CoA via artificial small RNAs in photosynthetic Synechocystis sp. PCC 6803

Current knowledge and recent advances in understanding metabolism of the model cyanobacteriumSynechocystissp. PCC 6803

Discovery of Cyanobacterial Natural Products Containing Fatty Acid Residues

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