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两种木霉菌株中肽菌素抗生素的定向生物合成。I. 发酵与分离。

Directed biosynthesis of peptaibol antibiotics in two Trichoderma strains. I. Fermentation and isolation.

作者信息

Leclerc G, Rebuffat S, Goulard C, Bodo B

机构信息

Laboratoire de Chimie des Substances Naturelles, URA 401 CNRS, Muséum National d'Histoire Naturelle, Paris, France.

出版信息

J Antibiot (Tokyo). 1998 Feb;51(2):170-7. doi: 10.7164/antibiotics.51.170.

DOI:10.7164/antibiotics.51.170
PMID:9544938
Abstract

Peptaibols are linear alpha-aminoisobutyric acid-containing peptide antibiotics originating from soil fungi mainly of the genus Trichoderma and biosynthesized in complex mixtures of closely related analogues by a polyenzymatic pathway. Addition of amino acids such as alpha-aminoisobutyric acid (Aib), glutamic acid or arginine, to the fermentation medium of two Trichoderma strains, T. harzianum and T. longibrachiatum, has been shown to result in the simplification of the natural peptaibol mixtures, leading in each case to the almost exclusive biosynthesis of a single peptide. Surprisingly, the obtained peptides are Aib-enriched, whether the added amino acid is Aib, Glu or Arg. By adding Aib to the fermentation medium of T. harzianum, two new Aib-rich peptaibols were isolated. Moreover, adding glutamic acid to the culture medium of T. longibrachiatum, which produces both neutral and acidic 20-residue peptaibols with either glutamine or glutamic acid at position 18, increases the production of the acidic peptides. However, arginine which is a positively charged amino acid generally absent from peptaibol sequences, is not incorporated in trichorzins when added to the fermentation medium of T. harzianum.

摘要

肽菌素是一类线性含α-氨基异丁酸的肽抗生素,主要源自木霉属土壤真菌,通过多酶途径在密切相关类似物的复杂混合物中生物合成。已表明,向哈茨木霉和长枝木霉这两种木霉菌株的发酵培养基中添加α-氨基异丁酸(Aib)、谷氨酸或精氨酸等氨基酸,会导致天然肽菌素混合物简化,每种情况下都会几乎专一性地生物合成单一肽。令人惊讶的是,无论添加的氨基酸是Aib、Glu还是Arg,所获得的肽都富含Aib。通过向哈茨木霉的发酵培养基中添加Aib,分离出了两种新的富含Aib的肽菌素。此外,向长枝木霉的培养基中添加谷氨酸,该菌株会产生在第18位带有谷氨酰胺或谷氨酸的中性和酸性20残基肽菌素,这会增加酸性肽的产量。然而,精氨酸是肽菌素序列中通常不存在的带正电荷氨基酸,当添加到哈茨木霉的发酵培养基中时,它不会掺入木霉素中。

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