气候变化领域集成服务门户(CCPortal): Genomic and Metabolite Profiling Reveal a Novel Streptomyces Strain, QHH-9511, from the Qinghai-Tibet Plateau

CCPortal

DOI	10.1128/spectrum.02764-22
	Genomic and Metabolite Profiling Reveal a Novel Streptomyces Strain, QHH-9511, from the Qinghai-Tibet Plateau
	Feng, Xi-Long; Zhang, Rui-Qi; Wang, Da-Cheng; Dong, Wei-Ge; Wang, Zhen-Xin; Zhai, Yi-Jie; Han, Wen-Bo; Yin, Xia; Tian, Junmian; Wei, Jing; Gao, Jin-Ming; Qi, Jianzhao
发表日期	2023
ISSN	2165-0497
卷号	11 期号:1
英文摘要	The prevalence of superbugs, represented by methicillin-resistant Staphylococcus aureus (MRSA), has become a serious clinical and public safety concern with rising incidence in hospitals. Polyketides with diverse chemical structures harbor many antimicrobial activities, including those of rifampin and rapamycin against MRSA. Streptomyces sp. QHH-9511 was isolated from a niche habitat in the Qinghai-Tibet Plateau and used to produce antibacterial metabolites. Herein, an integrated approach combining genome mining and metabolic analysis were employed to decipher the chemical origin of the antibacterial components with pigmented properties in strain QHH-9511, a novel Streptomyces species from a lichen symbiont on the Qinghai-Tibet Plateau. Genomic phylogeny assembled at the chromosome level revealed its unique evolutionary state. Further genome mining uncovered 36 candidate gene clusters, most of which were uncharacterized. Meanwhile, based on liquid chromatography coupled to diode array detection mass spectrometry, a series of granaticins, BSMs, chromones, phaeochromycins, and related molecules were discovered by using the Global Natural Product Social molecular networking platform. Subsequently, several pigment compounds were isolated and identified by high-resolution mass spectrometry and/or nuclear magnetic resonance, among which the structure-activity relationships of seven aromatic polyketides showed that the fused lactone ring of the C-2 carboxyl group could increase antibacterial activity. Genetic experiments indicated that all seven aromatic polyketides are a series of metabolic shunts produced by a single type II polyketide synthase (PKS) cluster. Comparative genomic analysis of granaticin producers showed that the granaticin gene cluster is widely distributed. This study provides an efficient method to combine genome mining and metabolic profiling techniques to uncover bioactive metabolites derived from specific habitats, while deepening our understanding of aromatic polyketide biosynthesis. IMPORTANCE Undescribed microorganisms from special habitats are being screened for anti-superbug drug molecules. In a project to screen actinomycetes for anti-MRSA activity, we isolated a Streptomyces strain from Qinghai Lake lichens. The phylogeny based on the genome assembled at the chromosome level revealed this strain's unique evolutionary state. The chemical origins of the antibacterial components with pigment properties in strain QHH-9511 were determined using an integrated approach combining genome mining and metabolic analysis. Further genome mining uncovered 36 secondary metabolite gene clusters, the majority of which were previously unknown. A series of aromatic compounds were discovered using molecular network analysis, separation, and extraction. Genetic experiments revealed that all seven aromatic polyketides are a series of metabolic shunts produced by a single cluster of type II PKSs. This study describes a method for identifying novel Streptomyces from specific habitats by combining genome mining with metabolic profiling techniques.
关键词	novel Streptomyces phylogenomic analysis aromatic polyketides type II PKS biosynthetic potential
英文关键词	BIOSYNTHETIC GENE-CLUSTER; POLYKETIDE SYNTHASE; VIOLACEORUBER TU22; GRANATICIN; EXPRESSION; DISCOVERY; SEQUENCE; PRODUCT; GTRI-02
WOS研究方向	Microbiology
WOS记录号	WOS:000910633800001
来源期刊	MICROBIOLOGY SPECTRUM
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/283123
作者单位	Northwest A&F University - China; Shangluo University
推荐引用方式 GB/T 7714	Feng, Xi-Long,Zhang, Rui-Qi,Wang, Da-Cheng,et al. Genomic and Metabolite Profiling Reveal a Novel Streptomyces Strain, QHH-9511, from the Qinghai-Tibet Plateau[J],2023,11(1).
APA	Feng, Xi-Long.,Zhang, Rui-Qi.,Wang, Da-Cheng.,Dong, Wei-Ge.,Wang, Zhen-Xin.,...&Qi, Jianzhao.(2023).Genomic and Metabolite Profiling Reveal a Novel Streptomyces Strain, QHH-9511, from the Qinghai-Tibet Plateau.MICROBIOLOGY SPECTRUM,11(1).
MLA	Feng, Xi-Long,et al."Genomic and Metabolite Profiling Reveal a Novel Streptomyces Strain, QHH-9511, from the Qinghai-Tibet Plateau".MICROBIOLOGY SPECTRUM 11.1(2023).