Activation of the Biosynthetic Gene Cluster in Streptomyces sp. YINM00050 Facilitated the Discovery of a Novel Benzoisochromanequinone

doi:10.6023/cjoc202506021

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (1): 295-299.DOI: 10.6023/cjoc202506021 Previous Articles Next Articles

链霉菌Streptomyces sp. YINM00050中基因簇激活发现苯并异色烷醌类新化合物

张媛^a^,^†, 郭莹^a^,^†, 杨明熹^b^,^†, 董葵^b, 赵立兴^a, 马玲^c^,^*(), 尹敏^a^,^*()

^a 云南大学医学院昆明 650091
^b 保山市人民医院云南保山 678000
^c 昆明理工大学附属医院云南省第一人民医院临床药学科昆明 650032

收稿日期:2025-06-16 修回日期:2025-07-25 发布日期:2025-09-03
通讯作者: 马玲, 尹敏
作者简介:
^† 共同第一作者
基金资助:
国家自然科学基金(82160674); 国家自然科学基金(82160673); 昆明理工大学医学联合专项(KUST-KH2022014Y); 省级医学研究中心开放课题(2023YJZX-YX02)

Activation of the Biosynthetic Gene Cluster in Streptomyces sp. YINM00050 Facilitated the Discovery of a Novel Benzoisochromanequinone

Zhang Yuan^a, Guo Ying^a, Yang Mingxi^b, Dong Kui^b, Zhao Lixing^a, Ma Ling^c^,^*(), Yin Min^a^,^*()

^a School of Medicine, Yunnan University, Kunming 650091
^b Baoshang Peoples Hospital, Baoshan, Yunnan 678000
^c Department of Clinical Pharmacy, Affiliated Hospital of Kunming University of Science and Technology, The First People’s Hospital of Yunnan Province, Kunming 650032

Received:2025-06-16 Revised:2025-07-25 Published:2025-09-03
Contact: Ma Ling, Yin Min
About author:
^† The authors contributed equally to this work
Supported by:
National Natural Science Foundation of China(82160674); National Natural Science Foundation of China(82160673); Medical Joint Project of Kunming University of Science and Technology(KUST-KH2022014Y); Open Project of Yunnan Clinical Medical Center(2023YJZX-YX02)

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Abstract

Through genome mining, a type II polyketide synthase (PKS) gene cluster was identified within the genome of Streptomyces sp. YINM00050. This gene cluster exhibits a high degree of similarity to the biosynthetic gene cluster responsible for the production of alnumycin, a benzoisochromanequinone (BIQ) compound. Nevertheless, no BIQs were isolated from the fermentations of the wild-type strain YINM00050 using various media. Subsequently, the global regulatory plasmid pSH152-tRNA-Asp-AUC was introduced into the wild-type strain, thereby generating the mutant strain YINM00050- tRNA. The subsequent fermentation of this mutant strain enabled the targeted isolation of BIQs. Moreover, a novel anti-tumor compound, alnumycin E, was identified.

Key words: genome mining, Endophytic Streptomyces, gene cluster activation, benzoisochromanequinone

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Zhang Yuan, Guo Ying, Yang Mingxi, Dong Kui, Zhao Lixing, Ma Ling, Yin Min. Activation of the Biosynthetic Gene Cluster in Streptomyces sp. YINM00050 Facilitated the Discovery of a Novel Benzoisochromanequinone[J]. Chinese Journal of Organic Chemistry, 2026, 46(1): 295-299.

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References 15

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Position	δ_C, type	δ_H, mult (J in Hz)
1	73.0, CH	5.58, dd (9.3, 3.5)
3	158.5, C	—
4	100.0, CH	5.60, s
4a	139.6, C	—
5	114.3, CH	7.13, s
5a	131.4, C	—
6	184.8, C	—
7	135.2, CH	6.99, s
8	144.8, C	—
9	187.8, C	—
9a	113.0, C	—
10	157.1, C	—
10a	122.4, C	—
11	34.9, CH₂	1.96~2.02, m, overlapped 1.48~1.55, m, overlapped
12	18.1, CH₂	1.53~1.60, m, overlapped 1.45~1.52, m, overlapped
13	13.8, CH₃	0.96, t (7.1)
14	20.4, CH₃	1.96, s
1'	97.3, CH	5.52, s
2'	54.2, CH₃	3.44, s
3'	54.3, CH₃	3.43, s
OH-10	—	12.25, s

Position	δ_C, type	δ_H, mult (J in Hz)
1	73.0, CH	5.58, dd (9.3, 3.5)
3	158.5, C	—
4	100.0, CH	5.60, s
4a	139.6, C	—
5	114.3, CH	7.13, s
5a	131.4, C	—
6	184.8, C	—
7	135.2, CH	6.99, s
8	144.8, C	—
9	187.8, C	—
9a	113.0, C	—
10	157.1, C	—
10a	122.4, C	—
11	34.9, CH₂	1.96~2.02, m, overlapped 1.48~1.55, m, overlapped
12	18.1, CH₂	1.53~1.60, m, overlapped 1.45~1.52, m, overlapped
13	13.8, CH₃	0.96, t (7.1)
14	20.4, CH₃	1.96, s
1'	97.3, CH	5.52, s
2'	54.2, CH₃	3.44, s
3'	54.3, CH₃	3.43, s
OH-10	—	12.25, s

Compound	HL-60	A549	SMMC-7721	MCF-7	SW480	BEAS-2B
1	0.26±0.01	4.61±0.04	0.53±0.02	1.94±0.11	1.72±0.11	>40
DDP	2.97±0.14	12.55±0.60	9.60±0.67	21.03±0.71	35.63±1.16	>40
Taxol	<0.008	<0.008	0.28±0.02	<0.008	<0.008	0.46±0.01

Compound	HL-60	A549	SMMC-7721	MCF-7	SW480	BEAS-2B
1	0.26±0.01	4.61±0.04	0.53±0.02	1.94±0.11	1.72±0.11	>40
DDP	2.97±0.14	12.55±0.60	9.60±0.67	21.03±0.71	35.63±1.16	>40
Taxol	<0.008	<0.008	0.28±0.02	<0.008	<0.008	0.46±0.01

链霉菌Streptomyces sp. YINM00050中基因簇激活发现苯并异色烷醌类新化合物

Activation of the Biosynthetic Gene Cluster in Streptomyces sp. YINM00050 Facilitated the Discovery of a Novel Benzoisochromanequinone

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