Discovery of Germicidin Glucuronides from Streptomyces sp. LZ35

doi:10.6023/cjoc202101036

Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (6): 2502-2506.DOI: 10.6023/cjoc202101036 Previous Articles Next Articles

NOTES

链霉菌LZ35中Germicidin糖苷的发现

史海霞^a, 李瑶瑶^b, 朱敬^a, 王浩鑫^a^,^*(), 沈月毛^a^,^b

a 山东大学微生物技术国家重点实验室山东青岛 266237
b 山东大学药学院天然产物化学生物学教育部重点实验室济南 250012

收稿日期:2021-01-21 修回日期:2021-02-10 发布日期:2021-02-26
通讯作者: 王浩鑫
基金资助:
国家重点研发计划项目(2019YFA0905400); 山东大学青年学者计划(2016WLJH31); 长江学者和创新团队发展计划(IRT_17R68)

Discovery of Germicidin Glucuronides from Streptomyces sp. LZ35

Haixia Shi^a, Yaoyao Li^b, Jing Zhu^a, Haoxin Wang^a(), Yuemao Shen^a^,^b

a State Key Laboratory of Microbial Technology, Shandong University, Qingdao, Shandong 266237
b Key Laboratory of Chemical Biology, Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan 250012

Received:2021-01-21 Revised:2021-02-10 Published:2021-02-26
Contact: Haoxin Wang
Supported by:
National Key Research and Development Program(2019YFA0905400); Young Scholars Program of Shandong University(2016WLJH31); Program for Changjiang Scholars and Innovative Research Team in University(IRT_17R68)

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Abstract

Two new germicidin glucuronides were isolated from the metabolites of Streptomyces sp. SR111, which is derived from Streptomyces sp. LZ35 through deletion of eight biosynthetic gene clusters by screening of culture media. The chemicla structures of 1 and 2 were determined to be germicidin A-4-O-β-D-glucuronide and germicidin D-4-O-β-D-glucuronide, respectively, by analysis of 1-D and 2-D NMR data and high resolution mass spectrometry. The antibacterial and antifungal activities of 1 and2were eveluated by disc diffusion assay, and they showed no inhibitory activity at 20 μg/disc. The cytotoxic activities of 1 and 2 were tested by methyl thiazolyl tetrazolium (MTT) colorimetric method, and they were inactive against the HepG2 (liver cancer) and HeLa (cervical cancer) cell lines. Remarkably, compounds 1 and 2 represent the first two germicidins with a glucuronic acid moiety, which expands the structural diversity of germicidins

Key words: Streptomyces, natural products, screening of culture media, germicidins

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Haixia Shi, Yaoyao Li, Jing Zhu, Haoxin Wang, Yuemao Shen. Discovery of Germicidin Glucuronides from Streptomyces sp. LZ35[J]. Chinese Journal of Organic Chemistry, 2021, 41(6): 2502-2506.

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Fig. & Tab. 4

References 13

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Position	1		2
Position	δ_H	δ_C	δ_H	δ_C
2		164.1 (s)		164.9 (s)
3		107.2 (s)		101.7 (s)
4		163.6 (s)		164.3 (s)
5	6.78 (s)	95.6 (d)	6.35 (s)	94.7 (d)
6		166.9 (s)		168.1 (s)
7	2.95~2.85 (m)	39.6 (d)	2.77~2.71 (m)	32.6 (d)
8	2.07~1.95 (m) 1.95~1.85 (m)	26.9 (t)	1.17 (d, J=6.8 Hz)	20.4 (q)
9	1.26 (t, J=7.6 Hz)	11.4 (q)	1.16 (d, J=6.8 Hz)	20.3 (q)
10	1.57 (d, J=6.8)	17.8 (q)	1.82 (s)	9.1 (q)
11	2.85~2.76 (m) 2.75~2.66 (m)	16.4 (t)
12	1.40 (t, J=7.2 Hz)	12.4 (q)
1ʹ	5.63 (d, J=7.2 Hz)	98.8 (d)	5.23 (d, J=7.5 Hz)	99.3d
2ʹ	3.72~3.67 (m)	72.8 (d)	3.31~3.26 (m)	73.2d
3ʹ	3.74~3.69 (m)	75.7 (d)	3.32~3.27 (m)	76.1d
4ʹ	3.83 (t, J=9.2 Hz)	71.2 (d)	3.39~3.34 (m)	71.7d
5ʹ	4.41 (d, J=10.0 Hz)	75.3 (d)	3.97 (d, J=9.5 Hz)	75.6d
6ʹ		170.1 (s)		170.5 (s)

Position	1		2
Position	δ_H	δ_C	δ_H	δ_C
2		164.1 (s)		164.9 (s)
3		107.2 (s)		101.7 (s)
4		163.6 (s)		164.3 (s)
5	6.78 (s)	95.6 (d)	6.35 (s)	94.7 (d)
6		166.9 (s)		168.1 (s)
7	2.95~2.85 (m)	39.6 (d)	2.77~2.71 (m)	32.6 (d)
8	2.07~1.95 (m) 1.95~1.85 (m)	26.9 (t)	1.17 (d, J=6.8 Hz)	20.4 (q)
9	1.26 (t, J=7.6 Hz)	11.4 (q)	1.16 (d, J=6.8 Hz)	20.3 (q)
10	1.57 (d, J=6.8)	17.8 (q)	1.82 (s)	9.1 (q)
11	2.85~2.76 (m) 2.75~2.66 (m)	16.4 (t)
12	1.40 (t, J=7.2 Hz)	12.4 (q)
1ʹ	5.63 (d, J=7.2 Hz)	98.8 (d)	5.23 (d, J=7.5 Hz)	99.3d
2ʹ	3.72~3.67 (m)	72.8 (d)	3.31~3.26 (m)	73.2d
3ʹ	3.74~3.69 (m)	75.7 (d)	3.32~3.27 (m)	76.1d
4ʹ	3.83 (t, J=9.2 Hz)	71.2 (d)	3.39~3.34 (m)	71.7d
5ʹ	4.41 (d, J=10.0 Hz)	75.3 (d)	3.97 (d, J=9.5 Hz)	75.6d
6ʹ		170.1 (s)		170.5 (s)

样品	HeLa	HepG2
1	>20	>20
2	>20	>20
多柔比星	1.05±0.12	1.32±0.28

样品	HeLa	HepG2
1	>20	>20
2	>20	>20
多柔比星	1.05±0.12	1.32±0.28

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链霉菌LZ35中Germicidin糖苷的发现

Discovery of Germicidin Glucuronides from Streptomyces sp. LZ35

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