Biosynthesis of Lasalocid. I

Westley, John; Evans, Ralph H.; Harvey, G.; Pitcher, Ross G.; Pruess, David L.; Stempel, Arthur; Berger, Jacob

doi:10.7164/antibiotics.27.288

Cited by 32 publications

(18 citation statements)

References 29 publications

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“…The results clearly exclude the latter two of the three mechanisms proposed for oxygen origin and stereochemistry for the C-1 to C-15 portion of the lasalocid A chain. Absence of oxygen labeling in the rest of the chain supports the biosynthetic proposal by Westley et al (34) shown in Fig. 6.…”

supporting

confidence: 75%

“…Lasalocid A 13 (also known as X537A) is an ionophoric antibiotic (32) from Streptotnyces lasaliensis which is effective against certain poultry infections (33). The carbon skeleton had already been shown to be assembled from acetate, propionate, and butyrate units (34). Three plausible biosynthetic mechanisms could account for the oxygen substituents and the overall stereochem5Granaticin is being studied in collaboration with Prof. H .…”

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confidence: 99%

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Biosynthetic studies using ¹⁸O isotope shifts in ¹³C nuclear magnetic resonance

Vederas¹

1982

Can. J. Chem.

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JOHN C. VEDERAS. Can. J. Chem. 60, 1637 (1982). Isotopic substitution with oxygen-18 induces an observable upfield shift in the 13C nmr positions ofdirectly-attached carbons, and in some cases, P-carbons. The magnitudes of these shifts range from about 0.05 ppm to 0.01 ppm, and are dependent on structure in an empirically predictable fashion. Incorporation of doubly labeled (I3C, 180) precursors into polyketides followed by I3C nmr analysis can identify carbon-oxygen bonds remaining intact during microbial biosynthesis. This technique has been applied to studies on antibiotics such as brefeldin A, cytochalasin B, granaticin, and lasalocid A, as well as aflatoxin precursors such as averufin, versicolorin A, and sterigmatocystin. JOHN C. VEDERAS. Can. J. Chem. 60, 1637 (1982). La substitution isotopique par de I'oxygkne-18 induit, en rmn du "C, un dkplacement chimique observable vers les hauts champs des positions des atomes de carbone qui leur sont directement liCs et, dans certains cas, des dkplacements des atomes de carbone en position p. L'ordre de grandeur de ces dkplacements varie de 0,OSppm 2 0.01 ppm et ils dkpendent d'une f a~o n empirique de la structure. L'incorporation de prkcurseurs doublement marquks (13C, 180) dans les polycktides suivie d'une analyse par rmn du I3C permet d'identifier les liaisons carbone-oxygene qui demeurent intactes durant la synthkse microbienne. On a utilise cette technique pour ktudier les antibiotiques tels la brefeldine A, la cytochalasine B, la granaticine et la lasalocide A de m&me que des prkcurseurs d'aflatoxine tels que I'avkrufine, la versicolorine A et la stkrigmatocystine.[Traduit par le journal]During the last decade the development of I3C nmr techniques in biosynthesis has elucidated the arrangement of precursor units in carbon skeletons of most classes of secondary metabolites (1). However, the mechanisms and sequence by which these units are linked remain largely speculative, partly because of lack of methods to follow changes in intermediate oxidation states. In response there is agrowing interest in determination of the biosynthetic fate of precursor hydrogens using 2H nmr (2) and of oxygens using mass spectrometry (3,4). The latter technique can detect both commonlyemployed stable isotopes of oxygen, I7O and IsO, but ascertaining the exact structure of the mass spectrometric fragments in partially-labeled polyoxygenated molecules is often difficult. Frequently preliminary specific labeling experiments or chemical degradations are necessary (4). Unlike 160 and IsO, oxygen-17 has a nuclear spin (512) and can be observed directly by nmr. Unfortunately its use in biological studies (5, 6) has been limited by low natural abundance (0.037%) and consequent expense, as well as by broadness of nmr signals due to its quadrupole and spin-spin coupling. Recently, investigations by Boyer and coworkers (7), Risley and Van Etten (8), Darensbourg et 01. (9), and our group (10) have confirmed the theoretical prediction (1 1) that the more abundant oxygen-18 (0.204%) can be in...

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supporting

confidence: 75%

mentioning

confidence: 99%

Biosynthetic studies using ¹⁸O isotope shifts in ¹³C nuclear magnetic resonance

Vederas¹

1982

Can. J. Chem.

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“…[6] Ein erster Vorschlag zum Biosynthesemechanismus stammte von Cane, Celmer und Westley und Mitarbeitern. [7] Das Cane-CelmerWestley-Modell sieht ein von einem Polyketid abgeleitetes Trien-Intermediat vor -das Prämonensin -, das in einer Reaktionskaskade aus S N 2-Ringöffnun-gen epoxidiert und cyclisiert wird (Schema 1). Diese Hypothese hat sich weitgehend durchgesetzt und wird durch experimentelle Ergebnisse ( 18 O 2 -Markierungsexperimente und Sequenzierungen des Genclusters) gestützt.…”

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Stereochemische Uniformität bei marinen Polyetherleitern: Folgerungen für Biosynthese und Struktur des Maitotoxins

Gallimore

Spencer

2006

Angewandte Chemie

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Ein Ring tanzt aus der Reihe: Polyetherleitern gehören zu den bekanntesten marinen Naturstoffen, nicht nur wegen ihrer faszinierenden Strukturen, sondern auch wegen ihrer charakteristischen Toxizität. Ein einfaches Modell für die Biosynthese der Polyetherleitern einschließlich des Maitotoxins (siehe Formel), der größten und giftigsten Spezies dieser Naturstoffklasse, wird beschrieben. Ob dessen Struktur bisher korrekt angegeben wurde, muss infrage gestellt werden.

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“…[6] A biosynthetic proposal was first put forward by Cane, Celmer, and Westley. [7] The Cane-Celmer-Westley model involves a polyketidederived triene intermediate, "premonensin", which is subsequently epoxidized and cyclized in a cascade of S N 2 epoxide openings (Scheme 1). This hypothesis has remained foremost and has received widespread acceptance.…”

mentioning

confidence: 99%

Stereochemical Uniformity in Marine Polyether Ladders—Implications for the Biosynthesis and Structure of Maitotoxin

Gallimore

Spencer

2006

Angew Chem Int Ed

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Odd one out: Marine polyether ladders are probably the most well‐known of all marine natural products, not only for their fascinating structures, but also for their characteristic toxicity. A very straightforward model for the biosynthesis of all known polyether ladders, including maitotoxin (the largest and most toxic of this structural family; see formula) is described, but is the structure of this giant molecule really known?

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Biosynthesis of Lasalocid. I

Cited by 32 publications

References 29 publications

Biosynthetic studies using ¹⁸O isotope shifts in ¹³C nuclear magnetic resonance

Biosynthetic studies using ¹⁸O isotope shifts in ¹³C nuclear magnetic resonance

Stereochemische Uniformität bei marinen Polyetherleitern: Folgerungen für Biosynthese und Struktur des Maitotoxins

Stereochemical Uniformity in Marine Polyether Ladders—Implications for the Biosynthesis and Structure of Maitotoxin

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Biosynthesis of Lasalocid. I

Cited by 32 publications

References 29 publications

Biosynthetic studies using 18O isotope shifts in 13C nuclear magnetic resonance

Biosynthetic studies using 18O isotope shifts in 13C nuclear magnetic resonance

Stereochemische Uniformität bei marinen Polyetherleitern: Folgerungen für Biosynthese und Struktur des Maitotoxins

Stereochemical Uniformity in Marine Polyether Ladders—Implications for the Biosynthesis and Structure of Maitotoxin

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Biosynthetic studies using ¹⁸O isotope shifts in ¹³C nuclear magnetic resonance

Biosynthetic studies using ¹⁸O isotope shifts in ¹³C nuclear magnetic resonance