Dataset Information

Overexpression of Global Regulator PbrlaeA Leads to the Discovery of New Polyketide in Fungus Penicillium Brocae HDN-12-143.

ABSTRACT: Overexpression of the PbrlaeA gene of the fungus Penicillium brocae HDN-12-143 resulted in the isolation of four compounds including fumigatin chlorohydrin (1), whose configuration has not been reported before, and one new compound iso-fumigatin chlorohydrin (2). All structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data, 13C NMR calculations, and ECD calculations. Compounds 1 and 2 exhibited cytotoxic activity against HL-60 with IC50 of 18.63 and 24.83 ?M.

SUBMITTER: Wang L

PROVIDER: S-EPMC7186497 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Overexpression of Global Regulator PbrlaeA Leads to the Discovery of New Polyketide in Fungus Penicillium Brocae HDN-12-143.

Wang Lu L Zhang Xianyan X Zhang Kaijin K Zhang Xiaomin X Zhu Tianjiao T Che Qian Q Zhang Guojian G Li Dehai D

Frontiers in chemistry 20200421

Overexpression of the PbrlaeA gene of the fungus Penicillium brocae HDN-12-143 resulted in the isolation of four compounds including fumigatin chlorohydrin (1), whose configuration has not been reported before, and one new compound iso-fumigatin chlorohydrin (2). All structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data, 13C NMR calculations, and ECD calculations. Compounds 1 and 2 exhibited cyt ...[more]

PMID: 32373583

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Project description:BackgroundSesame is a great reservoir of bioactive constituents and unique antioxidant components. It is widely used for its nutritional and medicinal value. The expanding demand for sesame seeds is putting pressure on sesame breeders to develop high-yielding varieties. A hybrid breeding strategy based on male sterility is one of the most effective ways to increase the crop yield. To date, little is known about the genes and mechanism underlying sesame male fertility. Therefore, studies are being conducted to identify and functionally characterize key candidate genes involved in sesame pollen development. Polyketide synthases (PKSs) are critical enzymes involved in the biosynthesis of sporopollenin, the primary component of pollen exine. Their in planta functions are being investigated for applications in crop breeding.ResultsIn this study, we cloned the sesame POLYKETIDE SYNTHASE A (SiPKSA) and examined its function in male sterility. SiPKSA was specifically expressed in sesame flower buds, and its expression was significantly higher in sterile sesame anthers than in fertile anthers during the tetrad and microspore development stages. Furthermore, overexpression of SiPKSA in Arabidopsis caused male sterility in transgenic plants. Ultrastructural observation showed that the pollen grains of SiPKSA-overexpressing plants contained few cytoplasmic inclusions and exhibited an abnormal pollen wall structure, with a thicker exine layer compared to the wild type. In agreement with this, the expression of a set of sporopollenin biosynthesis-related genes and the contents of their fatty acids and phenolics were significantly altered in anthers of SiPKSA-overexpressing plants compared with wild type during anther development.ConclusionThese findings highlighted that overexpression of SiPKSA in Arabidopsis might cause male sterility through defective pollen wall formation. Moreover, they suggested that SiPKSA modulates vibrant pollen development via sporopollenin biosynthesis, and a defect in its regulation may induce male sterility. Therefore, genetic manipulation of SiPKSA might promote hybrid breeding in sesame and other crop species.

Project description:Standard laboratory cultures have long been known to hinder activation of specific gene clusters which in turn hamper production of secondary metabolites with unique properties due to lack of innovation or the inability to trigger cryptic gene clusters' expression. Due to challenges related to the avoidance of the isolation of replicated metabolites, resistance-developing pathogens are to be addressed by the scientific community worldwide in order to progress with novel and potent compounds which could further be developed in the future for pharmaceutical usage. This study reports the isolation of novel cryptic antibiotics from a marine fungus Penicillium sp. BB1122 collected from Zhoushan coast by applying the "metal-stress" strategy, here referring to the heavy metal cobalt (6 mM). High-performance liquid chromatography-guided isolation of four novel and four known compounds belonging to the polyketide class has been carried out where their relative as well as absolute configurations have been determined using spectroscopic analysis techniques as well as by the comparison of theoretically calculated ECD spectrum and the experimental ECD spectrum, respectively. The structures of novel compounds 7 and 8 represent the first example of 2,5-dioxabicyclo[2.2.1]heptane pyrone backbone bearing a migrated polyene chain. The novel compounds 7, 8, and 5 exhibited impressive antibiotic properties against methicillin resistant Staphylococcus aureus (MRSA) with MIC value of around 0.5 and 1 μg/mL, respectively. Moreover, the new compounds 1, 7, and 8 displayed potent antibiotic activities with MIC values of around 4 μg/mL against the pathogenic Pseudomonas aeruginosa. Moreover, the MBC of the different potent compounds ranged from 1 to 128 μg/mL against MRSA, P. aeruginosa, and Klebsiella pneumoniae. In addition, the cytotoxic activities were also evaluated where new antibiotics 7 and 8 were not obviously harmful toward normal liver cell lines LO2, showing IC50 values above 100 μg/mL. As a consequence, the results from this study unveiled that cobalt stress is an effective strategy to discover novel antibiotics from microorganisms.

Dataset Information

Overexpression of Global Regulator PbrlaeA Leads to the Discovery of New Polyketide in Fungus Penicillium Brocae HDN-12-143.

Publications

Overexpression of Global Regulator PbrlaeA Leads to the Discovery of New Polyketide in Fungus <i>Penicillium Brocae</i> HDN-12-143.

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