Biosynthesis of fatty acids and related metabolites

Rawlings, Bernard J.

doi:10.1039/a815275y

Cited by 46 publications

(34 citation statements)

References 228 publications

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“…However, inhibition of root growth caused by palmitate and its low water solubility (log p ϭ 7.15) and the low root uptake of palmitoyl-CoA were limiting factors interfering with incorporation of these substrates. Labeling of the alkyl carbons, in a pattern consistent with the catalytic mechanism of fatty-acid synthase (31), was achieved only with D-[2-13 C]glucose (Fig. 2, D and F; and Fig.…”

Section: Resultsmentioning

confidence: 99%

Elucidation of the Biosynthetic Pathway of the Allelochemical Sorgoleone Using Retrobiosynthetic NMR Analysis

Dayan

Kagan

Rimando

2003

Journal of Biological Chemistry

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NMR analyses of the labeling pattern obtained using various 13 C-labeled precursors indicated that both the lipid tail and the quinone head of sorgoleone, the main allelopathic component of the oily root exudate of Sorghum bicolor, were derived from acetate units, but that the two moieties were synthesized in different subcellular compartments. The 16:3 fatty acid precursor of the tail is synthesized by the combined action of fatty-acid synthase and desaturases most likely in the plastids. It is then exported out of the plastids and converted to 5-pentadecatriene resorcinol by a polyketide synthase. This resorcinol intermediate was identified in root hair extracts. The lipid resorcinol intermediate is then methylated by a S-adenosylmethionine-dependent O-methyltransferase and subsequently dihydroxylated by a P450 monooxygenase to yield the reduced form of sorgoleone.Sorgoleone (2-hydroxy-5-methoxy-3-[(Z,Z)-8Ј,11Ј,14Ј-pentadecatriene]-p-benzoquinone) (1) is the main allelopathic component of the oily root exudate of sorghum (Sorghum bicolor (L.) Moench) ( Fig. 1) (1-3). The term sorgoleone is also used to describe a group of lipophilic p-benzoquinones structurally related to 1 that are also produced by sorghum roots having a hydroxy and a methoxy substitution at positions 2 and 5, respectively, and either a 15-or 17-carbon aliphatic tail with various degrees of unsaturation at position 3 (3).The primary mechanism of phytotoxic action of 1 is associated with inhibition of photosynthesis in higher plant systems by competing for the binding site of plastoquinone on photosystem II (4 -6). This lipophilic p-benzoquinone is also known to hinder electron transfer reactions involved in mitochondrial respiration and to inhibit the enzyme p-hydroxyphenylpyruvate dioxygenase (7,8).The herbicidal and allelopathic properties of 1 make isolation of the genes responsible for its biosynthesis desirable, as manipulation of those genes in sorghum or their introduction in other plant species could provide a better understanding of the role of 1 in plant-plant interaction and natural weed control. To identify the genes and characterize the enzymes they encode, it is necessary to determine the steps involved in the biosynthesis of 1. Little has been reported on this subject.Sorgoleone is found exclusively as a hydrophobic droplet exuding from the tips of root hairs (2), and a recent investigation of sorghum roots suggested that the production of 1 is compartmentalized in the highly physiologically active root hairs (9). The biosynthesis of secondary metabolites occurring in root hairs has not been studied in detail, although other specialized cells at the interface between a plant surface and its environment (i.e. trichomes) are known to produce unique secondary metabolites (10 -12).It has been postulated that the biosynthesis of 1 and related resorcinolic lipids is the result of the convergence of two pathways, namely the fatty acid biosynthetic pathway for the synthesis of the aliphatic tail and the activity of polyketide synthase-...

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Section: Resultsmentioning

confidence: 99%

Elucidation of the Biosynthetic Pathway of the Allelochemical Sorgoleone Using Retrobiosynthetic NMR Analysis

Dayan

Kagan

Rimando

2003

Journal of Biological Chemistry

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“…Stereochemistry of the Desaturation Steps-The stereoselectivity of the removal of two vicinal hydrogen atoms from the acyl chain during desaturation to give a cis double bond seems to be conserved in all organisms (1)(2)(3). Previous studies (12)(13)(14) have shown that it is the pro-R hydrogens that are abstracted at positions 9,10 then 12,13 by the action of the ⌬ 9 -and ⌬ 12 -desaturases, respectively, leaving the pro-S hydrogen at all the ethylenic sites (Fig.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Fatty Acid Elongation and Desaturation Steps in Fusarium lateritium by Quantitative Two-dimensional Deuterium NMR Spectroscopy in Chiral Oriented Media

Baillif

Robins

Feunteun

et al. 2009

Journal of Biological Chemistry

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The origin of hydrogen atoms during fatty acid biosynthesis in Fusarium lateritium has been quantified by isotope tracking close to natural abundance. Methyl linoleate was isolated from F. lateritium grown in natural abundance medium or in medium slightly enriched with labeled water, glucose, or acetate, and the 2 H incorporation was determined by quantitative 2 H-{ 1 H} NMR in isotropic and chiral oriented solvents. Thus, the individual ( 2 H/ 1 H) i ratio at each pro-R and pro-S hydrogen position of the CH 2 groups along the chain can be analyzed. These values allow the isotope redistribution coefficients (a ij ) that characterize the specific source of each hydrogen atom to be related to the nonexchangeable hydrogen atoms in glucose and to the medium water. In turn, these can be related to the stereoselectivity that operates during the introduction or removal of hydrogens along the fatty acid chain. First, at even CH 2 the pro-S hydrogen comes only from water by protonation, whereas the pro-R hydrogen is introduced partly via acetate but principally from water. Second, the nonexchangeable hydrogens of glucose (positions H-6,6 and H-1) are shown to be introduced to the odd CH 2 via the NAD(P)H pool used by both reductases involved in the elongation steps of the fatty acid chain. Third, it is proved that hydrogens removed at sites 9,10 and 12,13 during desaturation by ⌬ 9 -and ⌬ 12 -desaturases are pro-R, and that during these desaturation steps ␣-secondary kinetic isotope effects occur at the 9 and 12 positions and not at the 10 and 13 positions.Fatty acids are ubiquitous natural products involved in many key biological processes, including acting as components of membranes, as lipophilic modifiers, as fuel stores, and as precursors of intracellular messengers (1-3). Their biosynthesis, which is strictly conserved throughout higher organisms, can be separated into two parts as follows: the formation of the basic C16 unit, palmitoylCoA (C16:1), by the fatty-acid synthase complex (FAS) 2 and the subsequent modification of this chain by a range of elongases, desaturases, conjugases, hydroxylases, and epoxidases. Many of these steps involve stereoselective enzymatic reactions during which hydrogen atoms are inserted or eliminated.We have previously shown that this process leads to a distribution of 2 H in long chain fatty acids that is nonstatistical (4 -7). Thus, isotopic fractionation is seen to be introduced. Two features general to all organisms so far examined can be noted. First, the methylenic groups at even positions tend to be richer than those at odd positions. Second, one of the ethylenic groups present at the positions of desaturation is consistently impoverished relative to the methylenic sites, whereas the other is not.Thus, each hydrogen atom in the final product will have a ( 2 H/ 1 H) ratio that is representative of its initial origin, its passage through the FAS elongation steps, and its potential participation in post-elongation modification of the chain. To date, it has proved possible to exp...

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“…[8] Im Allgemeinen werden sowohl Polyketide als auch Fettsäuren durch sich wiederholende decarboxylierende Claisen-Thioester-Kondensationen einer aktivierten Acyl-Startereinheit mit von Malonyl-CoA abgeleiteten Verlängerungseinheiten aufgebaut (Schema 1). [9] An diesem Vorgang sind eine b-Ketoacylsynthase (KS), eine optionale (Malonyl-)Acyltransferase (MAT/AT) sowie ein phosphopantetheinyliertes Acyl-Carrier-Protein (ACP) oder CoA als Anker für die wachsende Kette beteiligt. Nach jedem Kettenverlängerungsschritt wird die b-Oxo-Funktion durch eine Ketoreduktase (KR), eine Dehydratase (DH) und eine Enoylreduktase (ER) weiter umgesetzt, wodurch letztlich ein vollständig gesättigtes Acyl-Rückgrat entsteht.…”

Section: Mechanismen Zum Kettenaufbauunclassified

“…Die Primärprodukte können im Anschluss weiter modifiziert werden. Trotz der auffallenden ¾hnlichkeiten ihrer Kettenfortpflanzungsmechanismen unterscheiden sich die PKS und FAS [9] deutlich und repräsentieren einen metabolischen Verzeigungspunkt zwischen Primär-und Sekundärmetabolismus. Die beiden Polyketide bilden eine der größten Naturstoffklassen.…”

Section: Mechanismen Zum Kettenaufbauunclassified

Die biosynthetische Grundlage der Polyketid‐Vielfalt

Hertweck

2009

Angewandte Chemie

205

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Molekulares Lego: Polyketide bilden eine äußerst vielfältige Gruppe von Naturstoffen mit faszinierenden Kohlenstoffgerüsten (siehe Beispiele), die aus einfachen Acyl‐Bausteinen synthetisiert werden. Das Zusammenspiel von Chemie, Biochemie und Genetik lieferte wichtige Einblicke in die Programmierung des Polyketid‐Aufbaus und die beteiligten, komplexen Enzymsysteme. Dieser Aufsatz behandelt aktuelle Entwicklungen auf diesem Forschungsgebiet.magnified imagePolyketide bilden eine der größten Naturstoffklassen. Viele dieser Verbindungen – oder Derivate davon – sind wichtige Therapeutika, aber viele sind auch berüchtigte, Lebensmittel verderbende Toxine oder Virulenzfaktoren. Besonders bemerkenswert ist, dass sich die Verbindungen dieser heterogenen Gruppe, zu denen Polyether, Polyene, Polyphenole, Makrolide und Endiine gehören, hauptsächlich von einem der einfachsten natürlichen Bausteine ableiten: Essigsäure. Chemische, genetische und biochemische Untersuchungen haben Aufschluss über die Biosyntheseprogramme gegeben, die zur enormen Strukturvielfalt von Polyketiden führen. Dieser Aufsatz behandelt kürzlich aufgeklärte Biosynthesemechanismen, nach denen höchst unterschiedliche und komplexe Moleküle synthetisiert werden.

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Biosynthesis of fatty acids and related metabolites

Cited by 46 publications

References 228 publications

Elucidation of the Biosynthetic Pathway of the Allelochemical Sorgoleone Using Retrobiosynthetic NMR Analysis

Elucidation of the Biosynthetic Pathway of the Allelochemical Sorgoleone Using Retrobiosynthetic NMR Analysis

Investigation of Fatty Acid Elongation and Desaturation Steps in Fusarium lateritium by Quantitative Two-dimensional Deuterium NMR Spectroscopy in Chiral Oriented Media

Die biosynthetische Grundlage der Polyketid‐Vielfalt

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