Incorporation and modification of fatty acids in cyanobacterial natural products biosynthesis

Leão, Pedro N.; Martins, Teresa P.; Abt, Kathleen; Reis, João P. A.; Figueiredo, Sandra A. C.; Castelo-Branco, Raquel; Freitas, Sara

doi:10.1039/d3cc00136a

“…Marine cyanobacteria are prolific producers of bioactive secondary metabolites with diverse structures, including polyketides, modified peptides and fatty acid derivatives such as fatty acid amides [15][16][17][18]. Here, we report for the first time the discovery and isolation of a cyanobacterial C16 monounsaturated fatty acid (1) and its hydroxy-containing analogue (2), which were previously reported in marine diatoms and a green alga, in addition to two other structurally related analogues (3)(4), all differing in their oxidation status.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, marine algae are known for their cytoprotective effects, and several secondary metabolites have been isolated and characterized as inducers of the Keap1/Nrf2−ARE pathway [13,14]. Marine cyanobacteria are a rich source of structurally diverse secondary metabolites that elicit a wide range of biological activities [15][16][17][18]. Several natural products containing an α,β-unsaturated carbonyl system have been isolated from marine benthic cyanobacteria and are reported to induce the activation of Nrf2, including anaenamides C and D (Hormoscilla sp.…”

Section: Introductionmentioning

confidence: 99%

Discovery and Anti-Inflammatory Activity of a Cyanobacterial Fatty Acid Targeting the Keap1/Nrf2 Pathway

Al-Awadhi,

Simon,

Liu

et al. 2023

Marine Drugs

3

0

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The monounsaturated fatty acid 7(E)-9-keto-hexadec-7-enoic acid (1) and three structurally related analogues with different oxidation states and degrees of unsaturation (2–4) were discovered from a marine benthic cyanobacterial mat collected from Delta Shoal, Florida Keys. Their structures were elucidated using NMR spectroscopy and mass spectrometry. The structure of 1 contained an α,β-unsaturated carbonyl system, a key motif required for the activation of the Keap1/Nrf2−ARE pathway that is involved in the activation of antioxidant and phase II detoxification enzymes. Compounds 1–4 were screened in ARE-luciferase reporter gene assay using stably transfected HEK293 cells, and only 1 significantly induced Nrf2 activity at 32 and 10 µM, whereas 2–4 were inactive. As there is crosstalk between inflammation and oxidative stress, subsequent biological studies were focused on 1 to investigate its anti-inflammatory potential. Compound 1 induced Nqo1, a well-known target gene of Nrf2, and suppressed iNos transcript levels, which translated into reduced levels of nitric oxide in LPS-activated mouse macrophage RAW264.7 cells, a more relevant model for inflammation. RNA sequencing was performed to capture the effects of 1 on a global level and identified additional canonical pathways and upstream regulators involved in inflammation and immune response, particularly those related to multiple sclerosis. A targeted survey of marine cyanobacterial samples from other geographic locations, including Guam, suggested the widespread occurrence of 1. Furthermore, the previous isolation of 1 from marine diatoms and green algae implied a potentially important ecological role across marine algal eukaryotes and prokaryotes. The previous isolation from sea lettuce raises the possibility of dietary intervention to attenuate inflammation and related disease progression.

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“…Lipids are of fundamental importance to all known living organisms as they serve as major structural components of cellular membranes, represent a main form of energy storage and constitute a central substrate pool for the primary and in many cases the secondary metabolism. [1,2] Additionally, lipids serve as signaling molecules and play key roles in biological processes ranging from influencing development processes in microorganisms [3] to mammalian immunology [4] and cancer progression. [5,6] Any imbalance in lipid homeostasis can therefore have severe consequences for individual organisms or whole ecosystems.…”

Section: Introductionmentioning

confidence: 99%

Structure Revision of a Widespread Marine Sulfonolipid Class Based on Isolation and Total Synthesis

Roman,

Meisinger,

Guillonneau

et al. 2024

Angew Chem Int Ed

4

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The cosmopolitan marine Roseobacter clade is of global biogeochemical importance. Members of this clade produce sulfur‐containing amino lipids (SALs) of importance for biofilm formation and marine surface colonization processes. Despite their physiological importance and abundance, SALs have only been explored through genomic mining approaches and lipidomic studies based on mass spectrometry, which left the relative and absolute structures of SALs unresolved hindering progress in biochemical and functional investigations. Here, we report the structural revision of a new group of SALs, which we named cysteinolides, using a combination of analytical techniques, isolation and degradation experiments and total synthetic efforts. Contrary to the previously proposed homotaurine‐based structures, cysteinolides are composed of an N,O‐acylated cysteinolic acid‐containing head group carrying various different (α‑hydroxy) carboxylic acids. We performed the first validated targeted‐network based analysis, which allowed us to map the distribution and structural diversity of cysteinolides across bacterial lineages. Beyond offering structural insights, our research provides SAL standards and validated analytical data. This information holds significance for forthcoming investigations into bacterial sulfonolipid metabolism and biogeochemical nutrient cycling within marine environments.

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“…Sie dienen als Hauptbestandteile von Zellmembranen, stellen eine wichtige Form der Energiespeicherung dar und bilden den zentralen Substratpool für den Primär-und in vielen Fällen auch den Sekundärstoffwechsel. [1,2] Darüber hinaus dienen Lipide als Signalmoleküle und spielen eine Schlüsselrolle bei biologischen Prozessen, die von der Beeinflussung von Entwicklungsprozessen in Mikroorganismen [3] bis hin zur Immunologie [4] von Säugetieren und der Krebsentstehung reichen. [5,6] Ein Ungleichgewicht in der Lipidhomöostase kann daher schwerwiegende Folgen für einzelne Organismen oder ganze Ökosysteme haben.…”

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Strukturrevision einer weit verbreiteten marinen Sulfonolipidklasse basierend auf deren Isolierung und Totalsynthese

Roman,

Meisinger,

Guillonneau

et al. 2024

Angewandte Chemie

0

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The cosmopolitan marine Roseobacter clade is of global biogeochemical importance. Members of this clade produce sulfur‐containing amino lipids (SALs) of importance for biofilm formation and marine surface colonization processes. Despite their physiological importance and abundance, SALs have only been explored through genomic mining approaches and lipidomic studies based on mass spectrometry, which left the relative and absolute structures of SALs unresolved hindering progress in biochemical and functional investigations. Here, we report the structural revision of a new group of SALs, which we named cysteinolides, using a combination of analytical techniques, isolation and degradation experiments and total synthetic efforts. Contrary to the previously proposed homotaurine‐based structures, cysteinolides are composed of an N,O‐acylated cysteinolic acid‐containing head group carrying various different (α‑hydroxy) carboxylic acids. We performed the first validated targeted‐network based analysis, which allowed us to map the distribution and structural diversity of cysteinolides across bacterial lineages. Beyond offering structural insights, our research provides SAL standards and validated analytical data. This information holds significance for forthcoming investigations into bacterial sulfonolipid metabolism and biogeochemical nutrient cycling within marine environments.

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Incorporation and modification of fatty acids in cyanobacterial natural products biosynthesis

Abstract: Cyanobacterial secondary metabolite biosynthesis often involves the use of a rich enzymatic arsenal for the incorporation and modification of fatty acid-derived moieties.

Cited by 5 publications

References 98 publications

Discovery and Anti-Inflammatory Activity of a Cyanobacterial Fatty Acid Targeting the Keap1/Nrf2 Pathway

Discovery and Anti-Inflammatory Activity of a Cyanobacterial Fatty Acid Targeting the Keap1/Nrf2 Pathway

Structure Revision of a Widespread Marine Sulfonolipid Class Based on Isolation and Total Synthesis

Strukturrevision einer weit verbreiteten marinen Sulfonolipidklasse basierend auf deren Isolierung und Totalsynthese

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