BIOSYNTHESIS OF THE MODIFIED PEPTIDE ANTIBIOTIC NOSIHEPTIDE IN STREPTOMYCES-ACTUOSUS
BIOSYNTHESIS OF THE MODIFIED PEPTIDE ANTIBIOTIC NOSIHEPTIDE IN STREPTOMYCES-ACTUOSUS
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DOI：
10.1021/ja00225a035
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发表时间：
1988-08-17
影响因子：
15
通讯作者：
FLOSS, HG
中科院分区：
文献类型：
--
作者：
HOUCK, DR;CHEN, LC;FLOSS, HG
在放射性和13 C标记的前体在Streptomyces actuosus中的饲养实验中研究了修饰的富硫肽抗生素那西肽（1）的生物合成。在广泛的化学位移分配之后，通过13 C NMR光谱分析1的13 C标记的样品。除了支持噻唑环和L-半胱氨酸部分来自半胱氨酸、L-苏氨酸和丁酸部分来自苏氨酸以及羟基谷氨酸部分来自谷氨酸的预期来源外，结果还表明脱氢丙氨酸部分是通过丝氨酸脱水产生的。吡啶环独特地由两个串联残基的“尾对尾”缩合形成。如双标记实验所证明的，吲哚酸部分通过色氨酸的新的分子内重排产生，其中羧基连接到吲哚的C2和α-色氨酸的C2上。碳和氨基氮被除去。只有吲哚环的C4位的羟甲基是通过C-甲基化衍生的，而不是通过4-甲基色氨酸。结果定义了1的假设肽前体的序列。
The biosynthesis of the modified, sulfur-rich peptide antibiotic nosiheptide (1) was studied in feeding experiments with radioactive and 13C-labeled precursors in Streptomyces actuosus. Following extensive chemical-shift assignments, 13C-labeled samples of 1 were analyzed by 13C NMR spectroscopy. In addition to supporting the expected origin of the thiazole ring and the L-cysteine moiety from cysteine, the L-threonine and butyrine moieties from threonine, and the hydroxyglutamate moiety from glutamate, the results demonstrated that the dehydroalanine moiety arises by dehydration of serine. The pyridine ring is formed uniquely by "tail-to-tail" condensation of two series residues. As demonstrated by a double-labeling experiment, the indolic acid moiety arises by a novel intramolecular rearrangement of tryptophan in which the carboxyl group is connected to C2 of the indole and the .alpha.-carbon and the amino nitrogen are eliminated. Only the hydroxymethyl group at C4 of the indole ring is derived by a C-methylation, but not via 4-methyltryptophan. The results define the sequence of a hypothetical peptide precursor of 1.