In vivo Studies on the Biosynthetic Pathway of Aureonuclemycin and Identification of Key Metabolites

doi:10.6023/cjoc202301012

Chinese Journal of Organic Chemistry ›› 2023, Vol. 43 ›› Issue (7): 2561-2566.DOI: 10.6023/cjoc202301012 Previous Articles Next Articles

NOTES

金核霉素生物合成途径的体内研究和关键代谢物鉴定

王飞^a, 金文兵^b, 侯现锋^b, 唐功利^a^,^b^,^*(), 潘海学^a^,^b^,^*()

^a国科大杭州高等研究院化学与材料科学学院杭州 310024
^b中国科学院上海有机化学研究所上海 200032

收稿日期:2022-11-11 修回日期:2023-02-24 发布日期:2023-03-17
通讯作者: 唐功利, 潘海学
基金资助:
国家自然科学基金(32070065)

In vivo Studies on the Biosynthetic Pathway of Aureonuclemycin and Identification of Key Metabolites

Fei Wang^a, Wenbing Jin^b, Xianfeng Hou^b, Gongli Tang^a^,^b(), Haixue Pan^a^,^b()

^aSchool of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024
^bShanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032

Received:2022-11-11 Revised:2023-02-24 Published:2023-03-17
Contact: Gongli Tang, Haixue Pan
Supported by:
National Natural Science Foundation of China(32070065)

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Abstract

On the basis of aureonuclemycin biosynthetic gene cluster obtained in the previous work, in-frame markerless deletion mutants of all genes were constructed, and the key genes that play a role in the biosynthesis of aureonuclemycin were identified. Two key aureonuclemycin-like compounds were successfully obtained from mutant and wild-type strains. According to the results of in vivo experiments, metabolite analysis and identification of key compounds, the possible biosynthetic pathway of aureonuclemycin was proposed.

Key words: nucleoside antibiotic, biosynthesis, aureonuclemycin

Cite this article

Fei Wang, Wenbing Jin, Xianfeng Hou, Gongli Tang, Haixue Pan. In vivo Studies on the Biosynthetic Pathway of Aureonuclemycin and Identification of Key Metabolites[J]. Chinese Journal of Organic Chemistry, 2023, 43(7): 2561-2566.

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Fig. & Tab. 7

References 6

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No.	δ_C	δ_H, Mult. (J in Hz)	HSQC	¹H-¹H COSY	HMBC	NOESY
2	154.8	7.84, s	C-2	—	C-4, C-6	H-2'
4	150.2	—	—	—	—	—
5	120.0	—	—	—	—	—
6	157.1	—	—	—	—	—
8	141.2	7.88, s	C-8	—	C-4, C-5	H-2', H-6', H-8'
1'	92.4	5.79, s	C-1'	H-2'	C-4, C-8, C-2', C-3'	H-2', H-3', H-4'
2'	82.1	4.53, s	C-2'	H-1', H-3'	C-1', C-3', C-4'	H-1', H-3', H-6'
3'	77.4	4.32, s	C-3'	H-2', H-4'	C-1', C-2', C-4'	H-1', H-2', H-4', H-5'_a,b
4'	81.2	4.62, s	C-4'	H-3', H-5'_a,b	C-3', C-6'	H-1', H-3', H-5'_a,b
5'_a,b	27.1	2.22~2.34, m	C-5'	H-4', H-6'	C-3', C-4', C-6', C-7'	H-3', H-4', H-6'
6'	71.5	3.88, dd (4.8, 11.5)	C-6'	H-5'_a,b	C-5', C-7', C-8', C-10'	H-8, H-8', H-9', H-5'_a,b
7'	96.7	—	—	—	—	—
8'	71.0	3.61, d (3.2)	C-8'	H-9'	C-7'	H-6', H-9', H-8
9'	73.9	4.55, s	C-9'	H-8', H-10'	C-7', C-8', C-10'	H-6', H-8', H-10'
10'	83.3	4.39, s	C-10'	H-9'	C-6', C-8', C-9', C-11'	H-9'
11'	177.6	—	—	—	—	—

No.	δ_C	δ_H, Mult. (J in Hz)	HSQC	¹H-¹H COSY	HMBC	NOESY
2	154.8	7.84, s	C-2	—	C-4, C-6	H-2'
4	150.2	—	—	—	—	—
5	120.0	—	—	—	—	—
6	157.1	—	—	—	—	—
8	141.2	7.88, s	C-8	—	C-4, C-5	H-2', H-6', H-8'
1'	92.4	5.79, s	C-1'	H-2'	C-4, C-8, C-2', C-3'	H-2', H-3', H-4'
2'	82.1	4.53, s	C-2'	H-1', H-3'	C-1', C-3', C-4'	H-1', H-3', H-6'
3'	77.4	4.32, s	C-3'	H-2', H-4'	C-1', C-2', C-4'	H-1', H-2', H-4', H-5'_a,b
4'	81.2	4.62, s	C-4'	H-3', H-5'_a,b	C-3', C-6'	H-1', H-3', H-5'_a,b
5'_a,b	27.1	2.22~2.34, m	C-5'	H-4', H-6'	C-3', C-4', C-6', C-7'	H-3', H-4', H-6'
6'	71.5	3.88, dd (4.8, 11.5)	C-6'	H-5'_a,b	C-5', C-7', C-8', C-10'	H-8, H-8', H-9', H-5'_a,b
7'	96.7	—	—	—	—	—
8'	71.0	3.61, d (3.2)	C-8'	H-9'	C-7'	H-6', H-9', H-8
9'	73.9	4.55, s	C-9'	H-8', H-10'	C-7', C-8', C-10'	H-6', H-8', H-10'
10'	83.3	4.39, s	C-10'	H-9'	C-6', C-8', C-9', C-11'	H-9'
11'	177.6	—	—	—	—	—

No.	δ_C	δ_H, Mult. (J in Hz)	HSQC	¹H-¹H COSY	HMBC
2	144.6	8.40, s	C-2	—	C-4, C-6
4	148.1	—	—	—	—
5	118.1	—	—	—	—
6	149.9	—	—	—	—
8	143.7	8.75, s	C-8	—	C-4, C-5
1'	90.1	6.15, d (9.5)	C-1'	H-2'	C-4, C-8, C-2'
2'	80.2	4.65, s	C-2'	H-1', H-3'	C-3', C-4'
3'	75.4	4.38, s	C-3'	H-2', H-4'	C-1', C-4'
4'	78.7	4.67~4.69, m	C-4'	H-3', H-5'	C-6'
5'_a,b	24.8	2.33~2.21, m	C-5'	H-4', H-6'	C-3', C-4', C-6', C-7'
6'	66.7	4.39, dd (5.2, 11.8)	C-6'	H-5'_a,b	C-5', C-10'
7'	93.8	—	—	—	—
8'	90.9	—	—	—	—
9'	74.0	4.29, d (1.4)	C-9'	H-10'	C-7', C-8'
10'	77.7	4.56, d (1.4)	C-10'	H-9'	C-6', C-8', C-9', C-11'
11'	172.4	—	—	—	—

No.	δ_C	δ_H, Mult. (J in Hz)	HSQC	¹H-¹H COSY	HMBC
2	144.6	8.40, s	C-2	—	C-4, C-6
4	148.1	—	—	—	—
5	118.1	—	—	—	—
6	149.9	—	—	—	—
8	143.7	8.75, s	C-8	—	C-4, C-5
1'	90.1	6.15, d (9.5)	C-1'	H-2'	C-4, C-8, C-2'
2'	80.2	4.65, s	C-2'	H-1', H-3'	C-3', C-4'
3'	75.4	4.38, s	C-3'	H-2', H-4'	C-1', C-4'
4'	78.7	4.67~4.69, m	C-4'	H-3', H-5'	C-6'
5'_a,b	24.8	2.33~2.21, m	C-5'	H-4', H-6'	C-3', C-4', C-6', C-7'
6'	66.7	4.39, dd (5.2, 11.8)	C-6'	H-5'_a,b	C-5', C-10'
7'	93.8	—	—	—	—
8'	90.9	—	—	—	—
9'	74.0	4.29, d (1.4)	C-9'	H-10'	C-7', C-8'
10'	77.7	4.56, d (1.4)	C-10'	H-9'	C-6', C-8', C-9', C-11'
11'	172.4	—	—	—	—

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金核霉素生物合成途径的体内研究和关键代谢物鉴定

In vivo Studies on the Biosynthetic Pathway of Aureonuclemycin and Identification of Key Metabolites

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