Metabolic Regulation of Two <i<pksCT</i< Gene Transcripts in <i<Monascus ruber</i< Impacts Citrinin Biosynthesis

Citrinin (CIT), a secondary metabolite produced by the filamentous fungi <i<Monascus</i< species, exhibits nephrotoxic, hepatotoxic, and carcinogenic effects in mammals, remarkably restricting the utilization of <i<Monascus</i<-derived products. CIT synthesis is mediated thro...
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Autor*in:	Yi He [verfasserIn] Lisha Zhu [verfasserIn] Xingxing Dong [verfasserIn] Aoran Li [verfasserIn] Suyin Xu [verfasserIn] Liling Wang [verfasserIn] Yanchun Shao [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	alternative splicing citrinin glycolysis lipid metabolism RNA interference

Übergeordnetes Werk:	In: Journal of Fungi - MDPI AG, 2015, 9(2023), 12, p 1174
Übergeordnetes Werk:	volume:9 ; year:2023 ; number:12, p 1174

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/jof9121174

Katalog-ID:	DOAJ098843214

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520			\|a Citrinin (CIT), a secondary metabolite produced by the filamentous fungi <i<Monascus</i< species, exhibits nephrotoxic, hepatotoxic, and carcinogenic effects in mammals, remarkably restricting the utilization of <i<Monascus</i<-derived products. CIT synthesis is mediated through the <i<pksCT</i< gene and modified by multiple genetic factors. Here, the regulatory effects of two <i<pksCT</i< transcripts, <i<pksCT</i<α, and <i<pksCT</i<β, generated via pre-mRNA alternative splicing (AS), were investigated using hairpin RNA (ihpRNA) interference, and their impact on CIT biosynthesis and the underlying mechanisms were assessed through chemical biology and transcriptome analyses. The CIT yield in ihpRNA-pksCTα and ihpRNA-pksCT (α + β) transformants decreased from 7.2 μg/mL in the wild-type strain to 3.8 μg/mL and 0.08 μg/mL, respectively. Notably, several genes in the CIT biosynthetic gene cluster, specifically <i<mrl3</i<, <i<mrl5</i<, <i<mrr1,</i< and <i<mrr5</i< in the ihpRNA-pksCT (α + β) transformant, were downregulated. Transcriptome results revealed that silencing <i<pksCT</i< has a great impact on carbohydrate metabolism, amino acid metabolism, lipid metabolism, and AS events. The key enzymes in the citrate cycle (TCA cycle) and glycolysis were significantly inhibited in the transformants, leading to a decrease in the production of biosynthetic precursors, such as acetyl-coenzyme-A (acetyl-coA) and malonyl-coenzyme-A (malonyl-coA). Furthermore, the reduction of CIT has a regulatory effect on lipid metabolism via redirecting acetyl-coA from CIT biosynthesis towards lipid biosynthesis. These findings offer insights into the mechanisms underlying CIT biosynthesis and AS in <i<Monascus</i<, thus providing a foundation for future research.
650		4	\|a alternative splicing
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700	0		\|a Liling Wang \|e verfasserin \|4 aut
700	0		\|a Yanchun Shao \|e verfasserin \|4 aut
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author_variant	y h yh l z lz x d xd a l al s x sx l w lw y s ys
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allfields	10.3390/jof9121174 doi (DE-627)DOAJ098843214 (DE-599)DOAJa629e3a8a1b5422781baf99db2f6d2f2 DE-627 ger DE-627 rakwb eng QH301-705.5 Yi He verfasserin aut Metabolic Regulation of Two <i<pksCT</i< Gene Transcripts in <i<Monascus ruber</i< Impacts Citrinin Biosynthesis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Citrinin (CIT), a secondary metabolite produced by the filamentous fungi <i<Monascus</i< species, exhibits nephrotoxic, hepatotoxic, and carcinogenic effects in mammals, remarkably restricting the utilization of <i<Monascus</i<-derived products. CIT synthesis is mediated through the <i<pksCT</i< gene and modified by multiple genetic factors. Here, the regulatory effects of two <i<pksCT</i< transcripts, <i<pksCT</i<α, and <i<pksCT</i<β, generated via pre-mRNA alternative splicing (AS), were investigated using hairpin RNA (ihpRNA) interference, and their impact on CIT biosynthesis and the underlying mechanisms were assessed through chemical biology and transcriptome analyses. The CIT yield in ihpRNA-pksCTα and ihpRNA-pksCT (α + β) transformants decreased from 7.2 μg/mL in the wild-type strain to 3.8 μg/mL and 0.08 μg/mL, respectively. Notably, several genes in the CIT biosynthetic gene cluster, specifically <i<mrl3</i<, <i<mrl5</i<, <i<mrr1,</i< and <i<mrr5</i< in the ihpRNA-pksCT (α + β) transformant, were downregulated. Transcriptome results revealed that silencing <i<pksCT</i< has a great impact on carbohydrate metabolism, amino acid metabolism, lipid metabolism, and AS events. The key enzymes in the citrate cycle (TCA cycle) and glycolysis were significantly inhibited in the transformants, leading to a decrease in the production of biosynthetic precursors, such as acetyl-coenzyme-A (acetyl-coA) and malonyl-coenzyme-A (malonyl-coA). Furthermore, the reduction of CIT has a regulatory effect on lipid metabolism via redirecting acetyl-coA from CIT biosynthesis towards lipid biosynthesis. These findings offer insights into the mechanisms underlying CIT biosynthesis and AS in <i<Monascus</i<, thus providing a foundation for future research. alternative splicing citrinin glycolysis lipid metabolism <i<Monascus ruber</i< RNA interference Biology (General) Lisha Zhu verfasserin aut Xingxing Dong verfasserin aut Aoran Li verfasserin aut Suyin Xu verfasserin aut Liling Wang verfasserin aut Yanchun Shao verfasserin aut In Journal of Fungi MDPI AG, 2015 9(2023), 12, p 1174 (DE-627)796588538 (DE-600)2784229-0 2309608X nnns volume:9 year:2023 number:12, p 1174 https://doi.org/10.3390/jof9121174 kostenfrei https://doaj.org/article/a629e3a8a1b5422781baf99db2f6d2f2 kostenfrei https://www.mdpi.com/2309-608X/9/12/1174 kostenfrei https://doaj.org/toc/2309-608X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2023 12, p 1174
spelling	10.3390/jof9121174 doi (DE-627)DOAJ098843214 (DE-599)DOAJa629e3a8a1b5422781baf99db2f6d2f2 DE-627 ger DE-627 rakwb eng QH301-705.5 Yi He verfasserin aut Metabolic Regulation of Two <i<pksCT</i< Gene Transcripts in <i<Monascus ruber</i< Impacts Citrinin Biosynthesis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Citrinin (CIT), a secondary metabolite produced by the filamentous fungi <i<Monascus</i< species, exhibits nephrotoxic, hepatotoxic, and carcinogenic effects in mammals, remarkably restricting the utilization of <i<Monascus</i<-derived products. CIT synthesis is mediated through the <i<pksCT</i< gene and modified by multiple genetic factors. Here, the regulatory effects of two <i<pksCT</i< transcripts, <i<pksCT</i<α, and <i<pksCT</i<β, generated via pre-mRNA alternative splicing (AS), were investigated using hairpin RNA (ihpRNA) interference, and their impact on CIT biosynthesis and the underlying mechanisms were assessed through chemical biology and transcriptome analyses. The CIT yield in ihpRNA-pksCTα and ihpRNA-pksCT (α + β) transformants decreased from 7.2 μg/mL in the wild-type strain to 3.8 μg/mL and 0.08 μg/mL, respectively. Notably, several genes in the CIT biosynthetic gene cluster, specifically <i<mrl3</i<, <i<mrl5</i<, <i<mrr1,</i< and <i<mrr5</i< in the ihpRNA-pksCT (α + β) transformant, were downregulated. Transcriptome results revealed that silencing <i<pksCT</i< has a great impact on carbohydrate metabolism, amino acid metabolism, lipid metabolism, and AS events. The key enzymes in the citrate cycle (TCA cycle) and glycolysis were significantly inhibited in the transformants, leading to a decrease in the production of biosynthetic precursors, such as acetyl-coenzyme-A (acetyl-coA) and malonyl-coenzyme-A (malonyl-coA). Furthermore, the reduction of CIT has a regulatory effect on lipid metabolism via redirecting acetyl-coA from CIT biosynthesis towards lipid biosynthesis. These findings offer insights into the mechanisms underlying CIT biosynthesis and AS in <i<Monascus</i<, thus providing a foundation for future research. alternative splicing citrinin glycolysis lipid metabolism <i<Monascus ruber</i< RNA interference Biology (General) Lisha Zhu verfasserin aut Xingxing Dong verfasserin aut Aoran Li verfasserin aut Suyin Xu verfasserin aut Liling Wang verfasserin aut Yanchun Shao verfasserin aut In Journal of Fungi MDPI AG, 2015 9(2023), 12, p 1174 (DE-627)796588538 (DE-600)2784229-0 2309608X nnns volume:9 year:2023 number:12, p 1174 https://doi.org/10.3390/jof9121174 kostenfrei https://doaj.org/article/a629e3a8a1b5422781baf99db2f6d2f2 kostenfrei https://www.mdpi.com/2309-608X/9/12/1174 kostenfrei https://doaj.org/toc/2309-608X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2023 12, p 1174
allfields_unstemmed	10.3390/jof9121174 doi (DE-627)DOAJ098843214 (DE-599)DOAJa629e3a8a1b5422781baf99db2f6d2f2 DE-627 ger DE-627 rakwb eng QH301-705.5 Yi He verfasserin aut Metabolic Regulation of Two <i<pksCT</i< Gene Transcripts in <i<Monascus ruber</i< Impacts Citrinin Biosynthesis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Citrinin (CIT), a secondary metabolite produced by the filamentous fungi <i<Monascus</i< species, exhibits nephrotoxic, hepatotoxic, and carcinogenic effects in mammals, remarkably restricting the utilization of <i<Monascus</i<-derived products. CIT synthesis is mediated through the <i<pksCT</i< gene and modified by multiple genetic factors. Here, the regulatory effects of two <i<pksCT</i< transcripts, <i<pksCT</i<α, and <i<pksCT</i<β, generated via pre-mRNA alternative splicing (AS), were investigated using hairpin RNA (ihpRNA) interference, and their impact on CIT biosynthesis and the underlying mechanisms were assessed through chemical biology and transcriptome analyses. The CIT yield in ihpRNA-pksCTα and ihpRNA-pksCT (α + β) transformants decreased from 7.2 μg/mL in the wild-type strain to 3.8 μg/mL and 0.08 μg/mL, respectively. Notably, several genes in the CIT biosynthetic gene cluster, specifically <i<mrl3</i<, <i<mrl5</i<, <i<mrr1,</i< and <i<mrr5</i< in the ihpRNA-pksCT (α + β) transformant, were downregulated. Transcriptome results revealed that silencing <i<pksCT</i< has a great impact on carbohydrate metabolism, amino acid metabolism, lipid metabolism, and AS events. The key enzymes in the citrate cycle (TCA cycle) and glycolysis were significantly inhibited in the transformants, leading to a decrease in the production of biosynthetic precursors, such as acetyl-coenzyme-A (acetyl-coA) and malonyl-coenzyme-A (malonyl-coA). Furthermore, the reduction of CIT has a regulatory effect on lipid metabolism via redirecting acetyl-coA from CIT biosynthesis towards lipid biosynthesis. These findings offer insights into the mechanisms underlying CIT biosynthesis and AS in <i<Monascus</i<, thus providing a foundation for future research. alternative splicing citrinin glycolysis lipid metabolism <i<Monascus ruber</i< RNA interference Biology (General) Lisha Zhu verfasserin aut Xingxing Dong verfasserin aut Aoran Li verfasserin aut Suyin Xu verfasserin aut Liling Wang verfasserin aut Yanchun Shao verfasserin aut In Journal of Fungi MDPI AG, 2015 9(2023), 12, p 1174 (DE-627)796588538 (DE-600)2784229-0 2309608X nnns volume:9 year:2023 number:12, p 1174 https://doi.org/10.3390/jof9121174 kostenfrei https://doaj.org/article/a629e3a8a1b5422781baf99db2f6d2f2 kostenfrei https://www.mdpi.com/2309-608X/9/12/1174 kostenfrei https://doaj.org/toc/2309-608X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2023 12, p 1174
allfieldsGer	10.3390/jof9121174 doi (DE-627)DOAJ098843214 (DE-599)DOAJa629e3a8a1b5422781baf99db2f6d2f2 DE-627 ger DE-627 rakwb eng QH301-705.5 Yi He verfasserin aut Metabolic Regulation of Two <i<pksCT</i< Gene Transcripts in <i<Monascus ruber</i< Impacts Citrinin Biosynthesis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Citrinin (CIT), a secondary metabolite produced by the filamentous fungi <i<Monascus</i< species, exhibits nephrotoxic, hepatotoxic, and carcinogenic effects in mammals, remarkably restricting the utilization of <i<Monascus</i<-derived products. CIT synthesis is mediated through the <i<pksCT</i< gene and modified by multiple genetic factors. Here, the regulatory effects of two <i<pksCT</i< transcripts, <i<pksCT</i<α, and <i<pksCT</i<β, generated via pre-mRNA alternative splicing (AS), were investigated using hairpin RNA (ihpRNA) interference, and their impact on CIT biosynthesis and the underlying mechanisms were assessed through chemical biology and transcriptome analyses. The CIT yield in ihpRNA-pksCTα and ihpRNA-pksCT (α + β) transformants decreased from 7.2 μg/mL in the wild-type strain to 3.8 μg/mL and 0.08 μg/mL, respectively. Notably, several genes in the CIT biosynthetic gene cluster, specifically <i<mrl3</i<, <i<mrl5</i<, <i<mrr1,</i< and <i<mrr5</i< in the ihpRNA-pksCT (α + β) transformant, were downregulated. Transcriptome results revealed that silencing <i<pksCT</i< has a great impact on carbohydrate metabolism, amino acid metabolism, lipid metabolism, and AS events. The key enzymes in the citrate cycle (TCA cycle) and glycolysis were significantly inhibited in the transformants, leading to a decrease in the production of biosynthetic precursors, such as acetyl-coenzyme-A (acetyl-coA) and malonyl-coenzyme-A (malonyl-coA). Furthermore, the reduction of CIT has a regulatory effect on lipid metabolism via redirecting acetyl-coA from CIT biosynthesis towards lipid biosynthesis. These findings offer insights into the mechanisms underlying CIT biosynthesis and AS in <i<Monascus</i<, thus providing a foundation for future research. alternative splicing citrinin glycolysis lipid metabolism <i<Monascus ruber</i< RNA interference Biology (General) Lisha Zhu verfasserin aut Xingxing Dong verfasserin aut Aoran Li verfasserin aut Suyin Xu verfasserin aut Liling Wang verfasserin aut Yanchun Shao verfasserin aut In Journal of Fungi MDPI AG, 2015 9(2023), 12, p 1174 (DE-627)796588538 (DE-600)2784229-0 2309608X nnns volume:9 year:2023 number:12, p 1174 https://doi.org/10.3390/jof9121174 kostenfrei https://doaj.org/article/a629e3a8a1b5422781baf99db2f6d2f2 kostenfrei https://www.mdpi.com/2309-608X/9/12/1174 kostenfrei https://doaj.org/toc/2309-608X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2023 12, p 1174
allfieldsSound	10.3390/jof9121174 doi (DE-627)DOAJ098843214 (DE-599)DOAJa629e3a8a1b5422781baf99db2f6d2f2 DE-627 ger DE-627 rakwb eng QH301-705.5 Yi He verfasserin aut Metabolic Regulation of Two <i<pksCT</i< Gene Transcripts in <i<Monascus ruber</i< Impacts Citrinin Biosynthesis 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Citrinin (CIT), a secondary metabolite produced by the filamentous fungi <i<Monascus</i< species, exhibits nephrotoxic, hepatotoxic, and carcinogenic effects in mammals, remarkably restricting the utilization of <i<Monascus</i<-derived products. CIT synthesis is mediated through the <i<pksCT</i< gene and modified by multiple genetic factors. Here, the regulatory effects of two <i<pksCT</i< transcripts, <i<pksCT</i<α, and <i<pksCT</i<β, generated via pre-mRNA alternative splicing (AS), were investigated using hairpin RNA (ihpRNA) interference, and their impact on CIT biosynthesis and the underlying mechanisms were assessed through chemical biology and transcriptome analyses. The CIT yield in ihpRNA-pksCTα and ihpRNA-pksCT (α + β) transformants decreased from 7.2 μg/mL in the wild-type strain to 3.8 μg/mL and 0.08 μg/mL, respectively. Notably, several genes in the CIT biosynthetic gene cluster, specifically <i<mrl3</i<, <i<mrl5</i<, <i<mrr1,</i< and <i<mrr5</i< in the ihpRNA-pksCT (α + β) transformant, were downregulated. Transcriptome results revealed that silencing <i<pksCT</i< has a great impact on carbohydrate metabolism, amino acid metabolism, lipid metabolism, and AS events. The key enzymes in the citrate cycle (TCA cycle) and glycolysis were significantly inhibited in the transformants, leading to a decrease in the production of biosynthetic precursors, such as acetyl-coenzyme-A (acetyl-coA) and malonyl-coenzyme-A (malonyl-coA). Furthermore, the reduction of CIT has a regulatory effect on lipid metabolism via redirecting acetyl-coA from CIT biosynthesis towards lipid biosynthesis. These findings offer insights into the mechanisms underlying CIT biosynthesis and AS in <i<Monascus</i<, thus providing a foundation for future research. alternative splicing citrinin glycolysis lipid metabolism <i<Monascus ruber</i< RNA interference Biology (General) Lisha Zhu verfasserin aut Xingxing Dong verfasserin aut Aoran Li verfasserin aut Suyin Xu verfasserin aut Liling Wang verfasserin aut Yanchun Shao verfasserin aut In Journal of Fungi MDPI AG, 2015 9(2023), 12, p 1174 (DE-627)796588538 (DE-600)2784229-0 2309608X nnns volume:9 year:2023 number:12, p 1174 https://doi.org/10.3390/jof9121174 kostenfrei https://doaj.org/article/a629e3a8a1b5422781baf99db2f6d2f2 kostenfrei https://www.mdpi.com/2309-608X/9/12/1174 kostenfrei https://doaj.org/toc/2309-608X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 9 2023 12, p 1174
language	English
source	In Journal of Fungi 9(2023), 12, p 1174 volume:9 year:2023 number:12, p 1174
sourceStr	In Journal of Fungi 9(2023), 12, p 1174 volume:9 year:2023 number:12, p 1174
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	alternative splicing citrinin glycolysis lipid metabolism <i<Monascus ruber</i< RNA interference Biology (General)
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container_title	Journal of Fungi
authorswithroles_txt_mv	Yi He @@aut@@ Lisha Zhu @@aut@@ Xingxing Dong @@aut@@ Aoran Li @@aut@@ Suyin Xu @@aut@@ Liling Wang @@aut@@ Yanchun Shao @@aut@@
publishDateDaySort_date	2023-01-01T00:00:00Z
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callnumber-first	Q - Science
author	Yi He
spellingShingle	Yi He misc QH301-705.5 misc alternative splicing misc citrinin misc glycolysis misc lipid metabolism misc <i<Monascus ruber</i< misc RNA interference misc Biology (General) Metabolic Regulation of Two <i<pksCT</i< Gene Transcripts in <i<Monascus ruber</i< Impacts Citrinin Biosynthesis
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topic_title	QH301-705.5 Metabolic Regulation of Two <i<pksCT</i< Gene Transcripts in <i<Monascus ruber</i< Impacts Citrinin Biosynthesis alternative splicing citrinin glycolysis lipid metabolism <i<Monascus ruber</i< RNA interference
topic	misc QH301-705.5 misc alternative splicing misc citrinin misc glycolysis misc lipid metabolism misc <i<Monascus ruber</i< misc RNA interference misc Biology (General)
topic_unstemmed	misc QH301-705.5 misc alternative splicing misc citrinin misc glycolysis misc lipid metabolism misc <i<Monascus ruber</i< misc RNA interference misc Biology (General)
topic_browse	misc QH301-705.5 misc alternative splicing misc citrinin misc glycolysis misc lipid metabolism misc <i<Monascus ruber</i< misc RNA interference misc Biology (General)
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
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title	Metabolic Regulation of Two <i<pksCT</i< Gene Transcripts in <i<Monascus ruber</i< Impacts Citrinin Biosynthesis
ctrlnum	(DE-627)DOAJ098843214 (DE-599)DOAJa629e3a8a1b5422781baf99db2f6d2f2
title_full	Metabolic Regulation of Two <i<pksCT</i< Gene Transcripts in <i<Monascus ruber</i< Impacts Citrinin Biosynthesis
author_sort	Yi He
journal	Journal of Fungi
journalStr	Journal of Fungi
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lang_code	eng
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publishDateSort	2023
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author_browse	Yi He Lisha Zhu Xingxing Dong Aoran Li Suyin Xu Liling Wang Yanchun Shao
container_volume	9
class	QH301-705.5
format_se	Elektronische Aufsätze
author-letter	Yi He
doi_str_mv	10.3390/jof9121174
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title_sort	metabolic regulation of two <i<pksct</i< gene transcripts in <i<monascus ruber</i< impacts citrinin biosynthesis
callnumber	QH301-705.5
title_auth	Metabolic Regulation of Two <i<pksCT</i< Gene Transcripts in <i<Monascus ruber</i< Impacts Citrinin Biosynthesis
abstract	Citrinin (CIT), a secondary metabolite produced by the filamentous fungi <i<Monascus</i< species, exhibits nephrotoxic, hepatotoxic, and carcinogenic effects in mammals, remarkably restricting the utilization of <i<Monascus</i<-derived products. CIT synthesis is mediated through the <i<pksCT</i< gene and modified by multiple genetic factors. Here, the regulatory effects of two <i<pksCT</i< transcripts, <i<pksCT</i<α, and <i<pksCT</i<β, generated via pre-mRNA alternative splicing (AS), were investigated using hairpin RNA (ihpRNA) interference, and their impact on CIT biosynthesis and the underlying mechanisms were assessed through chemical biology and transcriptome analyses. The CIT yield in ihpRNA-pksCTα and ihpRNA-pksCT (α + β) transformants decreased from 7.2 μg/mL in the wild-type strain to 3.8 μg/mL and 0.08 μg/mL, respectively. Notably, several genes in the CIT biosynthetic gene cluster, specifically <i<mrl3</i<, <i<mrl5</i<, <i<mrr1,</i< and <i<mrr5</i< in the ihpRNA-pksCT (α + β) transformant, were downregulated. Transcriptome results revealed that silencing <i<pksCT</i< has a great impact on carbohydrate metabolism, amino acid metabolism, lipid metabolism, and AS events. The key enzymes in the citrate cycle (TCA cycle) and glycolysis were significantly inhibited in the transformants, leading to a decrease in the production of biosynthetic precursors, such as acetyl-coenzyme-A (acetyl-coA) and malonyl-coenzyme-A (malonyl-coA). Furthermore, the reduction of CIT has a regulatory effect on lipid metabolism via redirecting acetyl-coA from CIT biosynthesis towards lipid biosynthesis. These findings offer insights into the mechanisms underlying CIT biosynthesis and AS in <i<Monascus</i<, thus providing a foundation for future research.
abstractGer	Citrinin (CIT), a secondary metabolite produced by the filamentous fungi <i<Monascus</i< species, exhibits nephrotoxic, hepatotoxic, and carcinogenic effects in mammals, remarkably restricting the utilization of <i<Monascus</i<-derived products. CIT synthesis is mediated through the <i<pksCT</i< gene and modified by multiple genetic factors. Here, the regulatory effects of two <i<pksCT</i< transcripts, <i<pksCT</i<α, and <i<pksCT</i<β, generated via pre-mRNA alternative splicing (AS), were investigated using hairpin RNA (ihpRNA) interference, and their impact on CIT biosynthesis and the underlying mechanisms were assessed through chemical biology and transcriptome analyses. The CIT yield in ihpRNA-pksCTα and ihpRNA-pksCT (α + β) transformants decreased from 7.2 μg/mL in the wild-type strain to 3.8 μg/mL and 0.08 μg/mL, respectively. Notably, several genes in the CIT biosynthetic gene cluster, specifically <i<mrl3</i<, <i<mrl5</i<, <i<mrr1,</i< and <i<mrr5</i< in the ihpRNA-pksCT (α + β) transformant, were downregulated. Transcriptome results revealed that silencing <i<pksCT</i< has a great impact on carbohydrate metabolism, amino acid metabolism, lipid metabolism, and AS events. The key enzymes in the citrate cycle (TCA cycle) and glycolysis were significantly inhibited in the transformants, leading to a decrease in the production of biosynthetic precursors, such as acetyl-coenzyme-A (acetyl-coA) and malonyl-coenzyme-A (malonyl-coA). Furthermore, the reduction of CIT has a regulatory effect on lipid metabolism via redirecting acetyl-coA from CIT biosynthesis towards lipid biosynthesis. These findings offer insights into the mechanisms underlying CIT biosynthesis and AS in <i<Monascus</i<, thus providing a foundation for future research.
abstract_unstemmed	Citrinin (CIT), a secondary metabolite produced by the filamentous fungi <i<Monascus</i< species, exhibits nephrotoxic, hepatotoxic, and carcinogenic effects in mammals, remarkably restricting the utilization of <i<Monascus</i<-derived products. CIT synthesis is mediated through the <i<pksCT</i< gene and modified by multiple genetic factors. Here, the regulatory effects of two <i<pksCT</i< transcripts, <i<pksCT</i<α, and <i<pksCT</i<β, generated via pre-mRNA alternative splicing (AS), were investigated using hairpin RNA (ihpRNA) interference, and their impact on CIT biosynthesis and the underlying mechanisms were assessed through chemical biology and transcriptome analyses. The CIT yield in ihpRNA-pksCTα and ihpRNA-pksCT (α + β) transformants decreased from 7.2 μg/mL in the wild-type strain to 3.8 μg/mL and 0.08 μg/mL, respectively. Notably, several genes in the CIT biosynthetic gene cluster, specifically <i<mrl3</i<, <i<mrl5</i<, <i<mrr1,</i< and <i<mrr5</i< in the ihpRNA-pksCT (α + β) transformant, were downregulated. Transcriptome results revealed that silencing <i<pksCT</i< has a great impact on carbohydrate metabolism, amino acid metabolism, lipid metabolism, and AS events. The key enzymes in the citrate cycle (TCA cycle) and glycolysis were significantly inhibited in the transformants, leading to a decrease in the production of biosynthetic precursors, such as acetyl-coenzyme-A (acetyl-coA) and malonyl-coenzyme-A (malonyl-coA). Furthermore, the reduction of CIT has a regulatory effect on lipid metabolism via redirecting acetyl-coA from CIT biosynthesis towards lipid biosynthesis. These findings offer insights into the mechanisms underlying CIT biosynthesis and AS in <i<Monascus</i<, thus providing a foundation for future research.
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title_short	Metabolic Regulation of Two <i<pksCT</i< Gene Transcripts in <i<Monascus ruber</i< Impacts Citrinin Biosynthesis
url	https://doi.org/10.3390/jof9121174 https://doaj.org/article/a629e3a8a1b5422781baf99db2f6d2f2 https://www.mdpi.com/2309-608X/9/12/1174 https://doaj.org/toc/2309-608X
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author2	Lisha Zhu Xingxing Dong Aoran Li Suyin Xu Liling Wang Yanchun Shao
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up_date	2024-07-03T19:32:30.651Z
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