红树林来源链霉菌中2-羟基苯基噻唑啉衍生物及其生物合成基因簇分析

doi:10.11978/2024073

热带海洋学报 ›› 2025, Vol. 44 ›› Issue (2): 64-72.doi: 10.11978/2024073CSTR: 32234.14.2024073

红树林来源链霉菌中2-羟基苯基噻唑啉衍生物及其生物合成基因簇分析

刘思妮¹^,²(), 白猛¹^,², 朱义广³, 罗小卫¹^,², 高程海¹^,², 刘永宏¹^,², 徐新亚¹^,²(), 蒋晓东¹^,²()

1.广西中医药大学海洋药物研究院, 广西南宁 530200
2.广西海洋药物重点实验室, 广西南宁 530200
3.广东省海洋药物重点实验室(中国科学院南海海洋研究所), 广东广州 510301

收稿日期:2024-04-02 修回日期:2024-05-21 出版日期:2025-03-10 发布日期:2025-04-11
通讯作者: 徐新亚, 蒋晓东
作者简介:
刘思妮(1999—), 女, 广西壮族自治区贵港市人, 硕士研究生。email: 1795263227@qq.com
基金资助:
广西科技基地和人才专项(Guike AD22035167); 广西自然科学基金项目(2023GXNSFBA026139); 广西自然科学基金项目(2023GXNSFAA026313); 广东省海洋药物重点实验室开放基金课题项目(LMM2022-4); 广西中医药大学博士科研启动基金项目(2021BS022); 广西中医药大学《桂派中医药传承创新团队》项目(2022A007); 广西八桂学者专项基金项目(05019055); 广西中医药大学第三批“岐黄工程”高层次人才团队培育项目(202407)

2-Hydroxyphenyl thiazoline derivatives and their biosynthetic gene clusters from the mangroves-derived Strepomyces ardesiacus

LIU Sini¹^,²(), BAI Meng¹^,², ZHU Yiguang³, LUO Xiaowei¹^,², GAO Chenghai¹^,², LIU Yonghong¹^,², XU Xinya¹^,²(), JIANG Xiaodong¹^,²()

1. Institute of Marine Drugs, Guangxi University of Chinese Medicine, Nanning 530200, China
2. Guangxi Key Laboratory of Marine Drugs, Nanning 530200, China
3. Guangdong Key Laboratory of Marine Materia Medica (South China Sea Institute of Oceanology, CAS), Guangzhou 510301, China

Received:2024-04-02 Revised:2024-05-21 Online:2025-03-10 Published:2025-04-11
Contact: XU Xinya, JIANG Xiaodong
Supported by:
Guangxi Science and Technology Base and Talent Special Project(Guike AD22035167); Natural Science Foundation of Guangxi Province(2023GXNSFBA026139); Natural Science Foundation of Guangxi Province(2023GXNSFAA026313); Open Project of Guangdong Key Laboratory of Marine Materia Medica(LMM2022-4); Initial Scientific Research Foundation of Introduced Doctors in 2021 of Guangxi University of Chinese Medicine(2021BS022); Guangxi University of Chinese Medicine “Guipai Traditional Chinese Medicine Inheritance and Innovation Team” Project(2022A007); Special Fund for Bagui Scholars of Guangxi(05019055); Guangxi University of Traditional Chinese Medicine the third batch of “Qhuang Project” high-level talent team cultivation project(202407)

摘要/Abstract

摘要：

文章探讨和分析了海南红树林沉积物来源链霉菌Streptomyces ardesiacus GXIMD 03502的次级代谢产物及相应生物合成基因簇。通过比对16S rDNA序列信息对菌株进行初步鉴定。综合运用多种色谱分离技术分离其次级代谢产物, 结合波谱数据分析与文献数据比对确定化合物的结构。从该链霉菌中获得5个2-羟基苯基噻唑啉衍生物, 经鉴定分别为 (+)-(S)-pulicatin G (1)、pulicatin A (2)、aerugine (3)、pulicatin F (4) 和 (+)-(S)-dihydraeruginoic acid (5)。采用Illumina novaseq 6000技术对菌株进行基因组测序, 利用生物信息学技术分析、定位及注释负责合成相应化合物的基因簇, 并推导其生物合成途径。该菌株基因组分析结果表明其包含31个次级代谢生物合成基因簇, 其中基因簇11可能参与2-羟基苯基噻唑啉衍生物的生物合成, 并推导了该衍生物的合成途径。

关键词: 红树林放线菌, 链霉菌, 2-羟基苯基噻唑啉, 生物合成基因簇

Abstract:

In order to identify secondary metabolites and analyze the corresponding biosynthetic gene clusters, the strain GXIMD 03502, isolated from the mangroves in Hainan, was studied. The strain was identified by comparing the 16S rDNA sequence. The secondary metabolites were separated by various chromatographic separation techniques, and their structures were determined by spectral data analysis and literature comparison. Five 2-hydroxyphenylthiazoline derivatives were isolated from this strain and identified as (+)-(S)-pulicatin G (1), pulicatin A (2), aerugine (3), pulicatin F (4), and (+)-(S)-dihydraeruginoic acid (5). At the same time, the genomic DNA of the strain was obtained by Illumina novaseq 6000 sequencing technology. The bioinformatic approach was employed to annotate the biosynthetic gene cluster and deduce the biosynthetic pathways of the compounds. The analysis results of the whole genome DNA sequence indicated that it contained 31 secondary metabolic biosynthetic gene clusters, and revealed that cluster 11 may be responsible for the biosynthesis of 2-hydroxyphenylthiazoline derivatives. This study provided a mangroves-derived S. ardesiacus GXIMD 03502 to produce 2-hydroxyphenylthiazoline derivatives, and the whole genome sequence of this strain laid a foundation for the exploration of its secondary metabolites.

Key words: mangroves-derived actinomycetes, Strepomyces ardesiacus, 2-hydroxyphenylthiazolineine, biosynthetic gene cluster

中图分类号:

P735.4

刘思妮, 白猛, 朱义广, 罗小卫, 高程海, 刘永宏, 徐新亚, 蒋晓东. 红树林来源链霉菌中2-羟基苯基噻唑啉衍生物及其生物合成基因簇分析[J]. 热带海洋学报, 2025, 44(2): 64-72.

LIU Sini, BAI Meng, ZHU Yiguang, LUO Xiaowei, GAO Chenghai, LIU Yonghong, XU Xinya, JIANG Xiaodong. 2-Hydroxyphenyl thiazoline derivatives and their biosynthetic gene clusters from the mangroves-derived Strepomyces ardesiacus[J]. Journal of Tropical Oceanography, 2025, 44(2): 64-72.

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参考文献 21

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编号	类型	大小/kb	相似基因簇	相似度/%
1	RiPP-like	10.2	informatipeptin	42
2	T3PKS	41.2	alkylresorcinol	100
3	betalactone	27.9	/	/
4	Terpene	21.0	albaflavenone	100
5	Phosphonate-ladderane-Ⅰ PKS	67.2	amycomicin	87
6	Terpene	22.7	isorenieratene	62
7	indole	21.1	5-dimethylallylindole-3-acetonitrile	100
8	terpene	23.9	/	/
9	NRP-metallophore	63.0	coelibactin	100
10	NRP-metallophore	58.3	scabichelin	100
11	Ⅰ PKS - Ⅲ PKS-NRPS	95.3	thiazostatin/watasemycin	100
12	T3PKS	41.1	flaviolin	100
13	melanin	10.5	istamycin	5
14	NI-siderophore	11.8	desferrioxamin B and E	83
15	T1PKS-other	60.6	macrotermycins	65
16	terpene	22.2	geosmin	100
17	NRPS	35.4	ibomycin	12
18	Ⅲ PKS	41.2	germicidin	100
19	oligosaccharide	24.9	vancomycin glucose	42
20	Ⅱ PKS	72.5	WS-5995	69
21	NI-siderophore	11.9	/	/
22	terpene	26.7	hopene	100
23	lanthipeptide-class-iii	22.8	SapB	100
24	ectoine	10.4	ectoine	100
25	NRPS	25.9	paulomycin	13
26	terpene	20.9	azinomycin B	6
27	T2PKS	70.1	spore pigment	66
28	NRPS	53.2	detoxin S1	33
29	T1PKS	38.5	butyrolactol A	80
30	T1PKS-terpene	43.3	azalomycin F3a	32
31	T1PKS	14.3	ECO-0501	14

基因	氨基酸长度	同源蛋白	同一性/相似性/%	推测的基因功能
orf1	440	S. venezuelae ATCC10712 sven0503 (CCA53790)	77/81	AMP-ligase
orf2	421	S. venezuelae ATCC10712 sven0504 (CCA53791)	83/87	Na+/H+ antiporter
orf3	647	S. venezuelae ATCC10712 sven0505 (CCA53792)	85/88	AfsR-family regulator
orf4	455	S. venezuelae ATCC10712 sven0506 (CCA53793)	79/85	Salicylate synthase
orf5	282	S. venezuelae ATCC10712 sven0507 (CCA53794)	85/91	TetR-family regulator
orf6	390	S. venezuelae ATCC10712 sven0508 (CCA53795)	75/81	Reductase
orf7	228	S. venezuelae ATCC10712 sven0509 (CCA53796)	90/94	TetR-family regulator
orf8	532	S. venezuelae ATCC10712 sven0510 (CCA53797)	85/90	Salicyl-AMP-ligase
orf9	265	S. venezuelae ATCC10712 sven0511 (CCA53798)	74/80	Thioesterase
orf10	1517	S. venezuelae ATCC10712 sven0512 (CCA53799)	76/82	NRPS
orf11	569	S. venezuelae ATCC10712 sven0513 (CCA53800)	91/95	ABC transporter permease/ATPase
orf12	613	S. venezuelae ATCC10712 sven0514 (CCA53801)	89/93	ABC transporter permease/ATPase
orf13	534	S. venezuelae ATCC10712 sven0515 (CCA53802)	89/94	Radical SAM methyltransferase
orf14	383	S. venezuelae ATCC10712 sven0516 (CCA53803)	78/80	Reductase
orf15	1829	S. venezuelae ATCC10712 sven0517 (CCA53804)	84/89	NRPS

红树林来源链霉菌中2-羟基苯基噻唑啉衍生物及其生物合成基因簇分析

2-Hydroxyphenyl thiazoline derivatives and their biosynthetic gene clusters from the mangroves-derived Strepomyces ardesiacus

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