Geranylation of Cyclic Dipeptides and Naphthols by the Fungal Prenyltransferase CdpC3PT_F253G.

IF 2.6 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY ChemBioChem Pub Date : 2024-11-14 DOI:10.1002/cbic.202400787
Dan Li, Yi Wang, Yuanyuan Xu, Hongping Long, Wenqing Min, Shangfeng Gao, Shu-Ming Li, Xia Yu
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Abstract

Prenyl modification often improves the biological activities of compounds. Prenyltransferases have attracted attention as environmentally friendly biocatalysts for catalyzing prenyl modification of compounds. Compared to dimethylallyl modifications, research on geranyl modifications is relatively limited. To enrich biocatalytic toolboxes for generating potentially bioactive geranylated derivatives, this study developed methodologies to synthesize two types of geranylated compounds, i. e., geranylated tryptophan-containing cyclic dipeptides and geranylated naphthols, employing the F253G mutant of CdpC3PT, a cyclic dipeptide prenyltransferase from Neosartorya fischeri. The cyclic dipeptides (1-3) were transformed into C7-geranylated products (1G1-3G1), whereas 1-naphthol (4) and derivatives (5-6) yielded C4-geranylated products (4G1-6G1) and 2,7-dihydroxynaphthalene (7) generated a C3-geranylated product (7G1). All seven substrates and their geranylated products underwent antibacterial efficacy testing against Bacillus subtilis. Among them, five geranylated compounds (2G1 and 4G1-7G1) demonstrated antibacterial efficacies against Bacillus subtilis, with MIC values ranging from 4 to 32 μg/mL, surpassing their non-geranylated precursors. This research broadens the tools of geranyl-modifying biocatalysts, illustrates a case for developing highly efficient or function-altered biocatalysts and showcases the potential of prenyltransferases in the biosynthesis of bioactive small molecules.

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真菌异戊烯基转移酶 CdpC3PT_F253G 对环状二肽和萘酚的香叶酯化作用。
预烯基修饰通常能提高化合物的生物活性。异戊烯基转移酶作为催化化合物异戊烯基修饰的环境友好型生物催化剂备受关注。与二甲基烯丙基修饰相比,有关香叶基修饰的研究相对有限。为了丰富生物催化工具箱,以生成具有潜在生物活性的香叶酯化衍生物,本研究利用来自 Neosartorya fischeri 的环二肽前基转移酶 CdpC3PT 的 F253G 突变体,开发了合成两类香叶酯化化合物的方法,即香叶酯化的含色氨酸环二肽和香叶酯化的萘酚。环状二肽(1-3)转化为 C7 -geranylated 产物(1G1-3G1),而 1-萘酚(4)及其衍生物(5-6)产生 C4 -geranylated 产物(4G1-6G1),2,7-二羟基萘(7)产生 C3 -geranylated 产物(7G1)。所有七种底物及其香叶酯化产物都对枯草杆菌进行了抗菌效果测试。其中,有五种香叶酯化化合物(2G1 和 4G1-7G1)对枯草杆菌具有抗菌效果,其 MIC 值从 4 μg/mL 到 32 μg/mL,超过了它们的非香叶酯化前体。这项研究拓宽了香叶酯修饰生物催化剂的工具,说明了开发高效或功能改变的生物催化剂的案例,并展示了前酰转移酶在生物活性小分子生物合成中的潜力。
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来源期刊
ChemBioChem
ChemBioChem 生物-生化与分子生物学
CiteScore
6.10
自引率
3.10%
发文量
407
审稿时长
1 months
期刊介绍: ChemBioChem (Impact Factor 2018: 2.641) publishes important breakthroughs across all areas at the interface of chemistry and biology, including the fields of chemical biology, bioorganic chemistry, bioinorganic chemistry, synthetic biology, biocatalysis, bionanotechnology, and biomaterials. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies, and supported by the Asian Chemical Editorial Society (ACES).
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