Isolation, Structure Elucidation, and Biosynthesis of a Cysteate-Containing Nonribosomal Peptide in Streptomyces lincolnensis
Isolation, Structure Elucidation, and Biosynthesis of a Cysteate-Containing Nonribosomal Peptide in Streptomyces lincolnensis
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林肯链霉菌中含半胱氨酸的非核糖体肽的分离、结构解析和生物合成
DOI：
10.1021/acs.joc.8b00044
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发表时间：
2018
影响因子：
3.6
通讯作者：
Liu Wen
中科院分区：
文献类型：
--
作者：
Wang Min;Chen D;an;Zhao Qunfei;Liu Wen
林可霉素A是一种临床上重要的林可酰胺类抗生素，具有抗革兰氏阳性菌的活性。在这里，我们报告这一点。林肯素类产生一种新的含有半胱酸的内酯产物，半胱胺(1)，它是由非核糖体多肽合成酶编程顺序组装苯乙酸、缬氨酸、半胱氨酸、苏氨酸、β-羟基亮氨酸和β-丙氨酸，然后在分子内环化形成内酯环而产生的。1的结构通过核磁共振和质谱图的组合分析确定，氨基酸的绝对构型由酸水解后的Marfey分析确定。在基因组OFS中定义了1的生物合成基因簇。生物信息学分析和活体发生研究中的连锁反应。此外，在体外实验中发现，Orfa是一种依赖于吡哆醛5‘-磷酸的蛋白，负责形成不寻常的半胱氨酸单位。含有半胱酸的非核糖体肽似乎广泛存在于各种链霉菌中，这项研究引起了人们对它们的内在功能的兴趣，但这些功能仍然知之甚少。
The speciesStreptomyces lincolnensisis known as a producer of lincomycin A, a clinically important lincosamide antibiotic with activity against Gram-positive bacteria. Here, we report thatS. lincolnensisproduces a new cysteate-containing lactone product, cysteoamide (1), which arises from nonribosomal peptide synthetase-programmed sequential assembly of the monomers phenylacetic acid, valine, cysteate, threonine, β-hydroxyleucine, and β-alanine and subsequent intramolecular cyclization to form a lactone ring. The structure of1was determined by combined analysis of NMR and MS spectra, while the amino acid absolute configurations in1were assigned by Marfey’s analysis following acid hydrolysis. The biosynthetic gene cluster of1was defined in the genome ofS. lincolnensisby bioinformatics analysis andin vivogenetic study. In addition,in vitroassay revealed that OrfA, a pyridoxal 5′-phosphate-dependent protein, is responsible for the formation of the unusual cysteate unit. Cysteate-containing nonribosomal peptides appear to be widely present in variousStreptomycesstrains, and this study generates interest in their intrinsic functions that remain poorly understood.