Genomic and Spectroscopic Signature-Based Discovery of Natural Macrolactams

化学 签名(拓扑) 自然(考古学) 计算生物学 生物 古生物学 几何学 数学
作者
Yern-Hyerk Shin,Ji Hyeon Im,Ilnam Kang,Eunji Kim,Sung Chul Jang,Eunji Cho,Daniel Shin,Sunghoon Hwang,Young Eun Du,Thanh-Hau Huynh,Kwang Wook Ko,Yoon‐Joo Ko,Sang‐Jip Nam,Takayoshi Awakawa,Jeeyeon Lee,Suckchang Hong,Ikuro Abe,Bradley S. Moore,William Fenical,Yeo Joon Yoon,Jang-Cheon Cho,Sang Kook Lee,Ki‐Bong Oh,Dong‐Chan Oh
出处
期刊:Journal of the American Chemical Society [American Chemical Society]
卷期号:145 (3): 1886-1896 被引量:7
标识
DOI:10.1021/jacs.2c11527
摘要

The logical and effective discovery of macrolactams, structurally unique natural molecules with diverse biological activities, has been limited by a lack of targeted search methods. Herein, a targeted discovery method for natural macrolactams was devised by coupling genomic signature-based PCR screening of a bacterial DNA library with spectroscopic signature-based early identification of macrolactams. DNA library screening facilitated the efficient selection of 43 potential macrolactam-producing strains (3.6% of 1,188 strains screened). The PCR amplicons of the amine-deprotecting enzyme-coding genes were analyzed to predict the macrolactam type (α-methyl, α-alkyl, or β-methyl) produced by the hit strains. 1H-15N HSQC-TOCSY NMR analysis of 15N-labeled culture extracts enabled macrolactam detection and structural type assignment without any purification steps. This method identified a high-titer Micromonospora strain producing salinilactam (1), a previously reported α-methyl macrolactam, and two Streptomyces strains producing new α-alkyl and β-methyl macrolactams. Subsequent purification and spectroscopic analysis led to the structural revision of 1 and the discovery of muanlactam (2), an α-alkyl macrolactam with diene amide and tetraene chromophores, and concolactam (3), a β-methyl macrolactam with a [16,6,6]-tricyclic skeleton. Detailed genomic analysis of the strains producing 1-3 identified putative biosynthetic gene clusters and pathways. Compound 2 displayed significant cytotoxicity against various cancer cell lines (IC50 = 1.58 μM against HCT116), whereas 3 showed inhibitory activity against Staphylococcus aureus sortase A. This genomic and spectroscopic signature-based method provides an efficient search strategy for new natural macrolactams and will be generally applicable for the discovery of nitrogen-bearing natural products.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
yujiashun完成签到,获得积分10
1秒前
NVSK完成签到,获得积分10
5秒前
公冶代丝发布了新的文献求助10
8秒前
Lorenzo完成签到 ,获得积分20
9秒前
枫之林完成签到,获得积分10
9秒前
充电宝应助木木夕云采纳,获得10
9秒前
万能图书馆应助wjs采纳,获得10
10秒前
鲍富完成签到,获得积分10
11秒前
kiki完成签到,获得积分10
11秒前
12秒前
诚心凝蝶完成签到,获得积分10
14秒前
ju123发布了新的文献求助10
15秒前
舟渡完成签到,获得积分20
15秒前
wuhao完成签到 ,获得积分10
15秒前
受伤的薯片完成签到 ,获得积分10
17秒前
坦率的千秋完成签到,获得积分20
18秒前
OMG完成签到,获得积分10
18秒前
Jackylee完成签到,获得积分10
22秒前
科研通AI2S应助marchon采纳,获得10
23秒前
23秒前
yujiashun发布了新的文献求助10
24秒前
wjs完成签到,获得积分20
25秒前
25秒前
25秒前
27秒前
evaporator发布了新的文献求助10
28秒前
完美世界应助舟渡采纳,获得30
28秒前
xiongdi521发布了新的文献求助10
29秒前
张津浩完成签到,获得积分10
29秒前
安静严青发布了新的文献求助10
29秒前
路之遥兮发布了新的文献求助10
30秒前
30秒前
30秒前
木木夕云发布了新的文献求助10
31秒前
32秒前
33秒前
acceleactor发布了新的文献求助10
33秒前
研友_8QqdO8完成签到 ,获得积分10
34秒前
xiongdi521完成签到,获得积分10
35秒前
36秒前
高分求助中
Manual of Clinical Microbiology, 4 Volume Set (ASM Books) 13th Edition 1000
Teaching Social and Emotional Learning in Physical Education 900
The three stars each : the Astrolabes and related texts 550
Boris Pesce - Gli impiegati della Fiat dal 1955 al 1999 un percorso nella memoria 500
Chinese-English Translation Lexicon Version 3.0 500
Recherches Ethnographiques sue les Yao dans la Chine du Sud 500
Two-sample Mendelian randomization analysis reveals causal relationships between blood lipids and venous thromboembolism 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 有机化学 工程类 生物化学 纳米技术 物理 内科学 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 电极 光电子学 量子力学
热门帖子
关注 科研通微信公众号,转发送积分 2399273
求助须知:如何正确求助?哪些是违规求助? 2100012
关于积分的说明 5294540
捐赠科研通 1827766
什么是DOI,文献DOI怎么找? 911100
版权声明 560078
科研通“疑难数据库(出版商)”最低求助积分说明 487001