106(P60) Acaterinの生合成研究(ポスター発表の部)
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概要
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Natural compounds having a 2-penten-4-olide skeleton have been found in a variety of organisms. This class of secondary metabolites can be grouped into two sub-classes depending on the oxidation state at C-3, i.e., C-3 hydroxyl (tetronic acid) and C-3 hydrogen. As far as the oxidation state at the C-4 and C-5 positions are concerned, further variations can be seen in these compounds. Acaterin (1), which belongs to the C-3 hydrogen sub-class, was isolated by Endo et al. from a culture broth of Pseudomonas sp. A 92. Herein we describe our recent findings on the biosynthesis of 1, obtained by feeding experiments of ^<13>C- and ^2H-labeled substrates. An olefinic analog of 1, named 4-dehydroacaterin (2), was newly isolated and characterized from a fermentation broth of P. sp. A 92 cultured in a medium supplemented with fatty acids. This 4,5-di-dehydro congener was shown to be the immediate biosynthetic precursor of 1. Feeding studies of ^<13>C- and ^2H-labeled C_8-, C_<10>- and C_<12>- fatty acids, in particular [2,3-^<13>C_2]decanoic acid, revealed that 1 is biosynthesized via coupling of a lactone moiety and octanoate, rather than via introduction of a C_3 unit at C-2 of a decanoic acid derivative. Further feeding studies of ^<13>C-labeled C_2-, C_3- and C_4-compounds indicated that glycerol is efficiently incorporated into the branched C_3 unit of 1 and 2. In addition, feeding studies of [1,1-^2H_2]- and sn-[3,3-^2H_2]-glycerols showed that two hydrogens at the sn-C-3 position are incorporated into the C-5 position of 1 and 2, whereas sn-C-1 hydrogens are completely lost during the transformation. These results suggest that 1 is biosynthesized via a glycerol metabolite having a carboxyl group at the sn-C-1 position such as glyceric acid. It is therefore conceivable that a tetronic acid type intermediates is involved in the biosynthesis of 1. The metabolic fate of the pro-R and pro-S hydrogens at the sn-C-3 position of glycerol during the formation of 2 has been investigated. Feeding studies of sn-(3R)- and sn-(3S)- (3-^2H)glycerols revealed that 5E hydrogen of 2 originates mainly from pro-R hydrogen at sn-C-3 of glycerol, while 5Z hydrogen comes mainly from pro-S. The findings imply that the immediate precursor of the C_3 branched unit of 1 is not pyruvate, but glyceric acid or its biological equivalent. On the basis of the present studies, we propose the following biosynthetic route to 1: an initial coupling of acetate (or malonate) and glyceric acid (or its derivative) leading to a 3,5-dihydroxy-2-penten-4-olide, substitution at C-2 of the lactone with octanoate, dehydration of 5-hydroxy group followed by reduction at C-3 leading to 2, and final reduction of 2 to 1. These data can be basically applicable to the biosynthesis of the other natural products of this class.
- 天然有機化合物討論会の論文
- 1999-09-01