Biosynthesis of isoxazolin-5-one and 3-nitropropanoic acid containing glucosides in juvenile Chrysomelina

Abstract

Stable-isotope-labeled precursors were used to establish the biosynthetic pathway leading from β-alanine towards isoxazolin-5-one glucoside 1 and its 3-nitropropanoate (3-NPA) ester 2 in Chrysomelina larvae. Both structural elements originate from sequestered plant-derived β-alanine or from propanoyl-CoA that is derived from the degradation of some essential amino acids, e.g. valine. β-Alanine is converted into 3-NPA and isoxazolinone 5 by consecutive oxidations of the amino group of β-Ala. Substituting the diphospho group of α-UDP-glucose with 5 generates the isoxazolin-5-one glucoside 1, which serves in the circulating hemolymph of the larva as a platform for esterification with 3-nitropropanoyl-CoA. The pathway was validated with larvae of Phaedon cochleariae, Chrysomela populi as well as Gastrophysa viridula.

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“…Further studies using metabolic labelling experiments showed that at least one of the nitrogens in the hydrazide moiety of fosfazinomycin A is derived from L-aspartic acid. Isotopic labelling studies have also been used to establish the biosynthesis of an isoxazolin-5-one glucoside 33 from β-alanine in Chrysomelina larvae 26. Both the 3-nitropropanoate and isoxazolinone moieties are formed from β-alanine by successive oxidations of the amino group.The commercially available tetracycline antibiotics have been shown to be substrates for the marine derived fungus Paecilomyces species 27.…”

A tale of four kingdoms – isoxazolin-5-one- and 3-nitropropanoic acid-derived natural products

“…65 In leaf beetles, similar trends were observed, as compounds 4 and 19 occur in amounts of 2 to 12 nmol mg À1 body weight in Phaedon cochleariae. 5,41 Analogously, these compounds were detected in millimolar concentrations in the eggs of these insects. 44 Within compound 4, both of the discussed moieties, 3-NPA and 3-isoxazolin-5-one, occur in the same molecule.…”

“…Consequently, the feeding experiments were repeated and expanded using leaf beetle larvae, which are easier to rear and treat, by applying stable isotope labeled compounds. 5 These studies revealed an incorporation of randomly re-assembled fragments of aspartate into compounds 4 and 19. In contrast, the intact incorporation of the essential amino acid valine was observed.…”

“…In addition, some studies revealed a fundamental relationship in the biosyntheses of the isoxazolinone heterocycle and 3-NPA in leaf beetles. 5,6 Whether in plants such relationships occur, producing both moieties, is not yet known. Since the prolonged consumption of seeds of some species of the genus Lathyrus (Leguminosae), e.g.…”

“…44 The same concentration ranges were determined for this compound in the larval hemolymph, 41 and show increasing tendencies with respect to the larval body weight. 5,41 To gain a comprehensive picture of the occurrence of 3-NPA and its derivatives in natural samples, it is of interest whether 3-NPA can be found only in its unaltered free form, or if it is found as a derivative, e.g. an ester as shown in many examples in Fig.…”