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Production of chain-extended cinnamoyl compounds by overexpressing two adjacent cluster-situated LuxR regulators in Streptomyces globisporus C-1027

ABSTRACT:

Natural products from microorganisms are important sources for drug discovery. With the development of high-throughput sequencing technology and bioinformatics, a large amount of uncharacterized biosynthetic gene clusters (BGCs) in microorganisms have been found, which show the potential for novel natural product production. 9 BGCs containing PKS and/or NRPS in Streptomyces globisporus C-1027 were transcriptionally low/silent under the experimental fermentation conditions, and the products of these clusters are unknown. Thus, we tried to activate these BGCs to explore cryptic products of this strain. We constructed the cluster-situated regulator overexpressing strains which contained regulator gene(s) under the control of the constitutive promoter ermE*p in S. globisporus C-1027. Overexpression of regulators in cluster 26 resulted in significant transcriptional upregulation of biosynthetic genes. With the separation and identification of products from the overexpressing strain OELuxR1R2, 3 ortho-methyl phenyl alkenoic acids (compounds 1-3) were obtained. Gene disruption showed that compounds 1 and 2 were completely abolished in the mutant GlaEKO, but were hardly affected by deletion of the genes orf3 or echA in cluster 26. The type II PKS biosynthetic pathway of chain-extended cinnamoyl compounds was deduced by bioinformatics analysis. This study showed that overexpression of the 2 adjacent cluster-situated LuxR regulator(s) is an effective strategy to connect the orphan BGC to its products.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase

SUBMITTER: Xingxing Li

PROVIDER: MTBLS5152 | MetaboLights | 2023-09-06

REPOSITORIES: MetaboLights

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Production of chain-extended cinnamoyl compounds by overexpressing two adjacent cluster-situated LuxR regulators in <i>Streptomyces globisporus</i> C-1027.

Li Xingxing X Ren Weicong W Li Yihong Y Shi Yuanyuan Y Sun Hongmin H Wang Lifei L Wu Linzhuan L Xie Yunying Y Du Yu Y Jiang Zhibo Z Hong Bin B

Frontiers in microbiology 20220803

PMID: 35992673

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	MTBLS5152	Other
	FILES	Other
	a_MTBLS5152_LC-MS_negative_reverse-phase_metabolite_profiling.txt	Txt
	files-all.json	Other
	i_Investigation.txt	Txt