Dynamic regulation of Monascus azaphilones biosynthesis by the binary MrPigE-MrPigF oxidoreductase system

Duan, Yali; Ma, Hongmin; Wei, Xuetuan; Li, Mu

doi:10.1007/s00253-022-12219-z

Cited by 7 publications

(7 citation statements)

References 38 publications

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“…In the ∆ mrpigF ::MrPigF-EGFP mutants, the biosynthesis of YMPs, particularly ankaflavin, monasfluore A, and monasfluore B, was enhanced compared to M7. However, the absence of the N-terminal SP in the ∆ mrpigF ::MrPigF ∆SP -EGFP strain led to a significant decrease in monascin and ankaflavin but a remarkable increase in monasfluore A. OMPs (rubropunctatin, monascorubrin) can be converted into YMPs (monascin, ankaflavin) in Monascus [ 19 ]. Thus, the two YMPs, monascin and ankaflavin, were significantly decreased in the ∆ mrpigF and ∆ mrpigF ::MrPigF ∆SP -EGFP strains, probably because of the absence of OMPs.…”

Section: Resultsmentioning

confidence: 99%

“…The mrpigE deletion strain loses the ability to yield OMPs [ 17 , 18 ]. In addition, in vitro and in vivo experiments demonstrate that MrPigE is responsible for converting OMPs (rubropunctatin, monascorubrin) into YMPs (monascin, ankaflavin) [ 19 ]. The gene mrpigF , encoding an FAD-dependent oxidoreductase in the final step of MPs synthesis, is directly responsible for yielding OMPs [ 5 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Exploring the Subcellular Localization of Monascus Pigments Biosynthases: Preliminary Unraveling of the Compartmentalization Mechanism

Xiong,

Wei,

Zhou

et al. 2024

JoF

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Monascus pigments (MPs), a class of secondary metabolites produced by Monascus spp., can be classified into yellow, orange, and red MPs according to their differences in the wavelength of the maximum absorption. However, the biosynthetic sequence and cellular biosynthesis mechanism of different MPs components are still not yet completely clear in Monascus spp. In this study, the subcellular localization of five MPs synthases was investigated using fluorescent protein fusion expression. The results revealed that the proteins encoded by the MPs biosynthetic gene cluster were compartmentalized in various subcellular locations, including the mitochondrial polyketide synthase MrPigA, cytosolic enzymes consisting of the ketoreductase MrPigC, the oxidoreductase MrPigE, and the monooxygenase MrPigN, and the cell-wall-bound oxidoreductase MrPigF. Moreover, the correct localization of MrPigF to the cell wall was crucial for the synthesis of orange MPs. Lastly, we discussed the compartmentalized biosynthetic pathway of MPs. This study will not only be helpful in clarifying the biosynthetic sequence and biosynthesis mechanism of different MPs but also provides new insights into the cellular biosynthesis of secondary metabolites in filamentous fungi.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exploring the Subcellular Localization of Monascus Pigments Biosynthases: Preliminary Unraveling of the Compartmentalization Mechanism

Xiong,

Wei,

Zhou

et al. 2024

JoF

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“…To develop an efficient helicase-BE molecular device, identification of the helicase subunits from M. purpureus HJ11 was necessary. Genome analysis of the strain revealed the presence of six proteins with high homology to the helicase subunits of Saccharomyces cerevisiae, 27 thus implying that these proteins (named MpHLC) may function as helicase subunits (Figure 2A).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Modular and Flexible Molecular Device for Simultaneous Cytosine and Adenine Base Editing at Random Genomic Loci in Filamentous Fungi

et al. 2023

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Random base editing is regarded as a fundamental method for accelerating the genomic evolution in both scientific research and industrial applications. In this study, we designed a modular interaction-based dual base editor (MIDBE) that assembled a DNA helicase and various base editors through dockerin/cohesin-mediated protein−protein interactions, resulting in a selfassembled MIDBE complex capable of editing bases at any locus in the genome. The base editing type of MIDBE can be readily controlled by the induction of cytidine or/and adenine deaminase gene expression. MIDBE exhibited the highest editing efficiency 2.3 × 10 3 times greater than the native genomic mutation rate. To evaluate the potential of MIDBE in genomic evolution, we developed a removable plasmid-based MIDBE tool, which led to a remarkable 977.1% increase of lovastatin production in Monascus purpureus HJ11. MIDBE represents the first biological tool for generating and accumulating base mutations in Monascus chromosome and also offers a bottom-up strategy for designing the base editor.

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“…Wild-type (WT) M. purpureus strain HJ11 used in this study was obtained from the China General Microbiological Culture Collection Center (CGMCC), accession number 25474 (Duan et al 2022c ). The strains OE:: mpSTE1 , CΔ mpSTE1 , and Δ mpSTE1 were deposited in CGMCC with accession numbers 27584, 27,585, and 27,586, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…Monacolin K, originally isolated from Monascus ruber (Endo 1979 ), is identical to the drug lovastatin independently discovered in Aspergillus terreus (Alberts et al 1980 ). As natural food colorants, Monascus azaphilone pigments have been widely used in Asia for centuries and possess a broad range of biological functions, such as anticancer, antimicrobial, and antiobesity bioactivities (Duan et al 2022c ; Huang et al 2023 ). Monascus -fermented products are estimated to be consumed by over one billion people daily, especially across Southeast Asia (Liu et al 2020 ).…”

Section: Introductionmentioning

confidence: 99%

The serine/threonine protein kinase MpSTE1 directly governs hyphal branching in Monascus spp.

Duan,

Chen,

Wang

et al. 2024

Appl Microbiol Biotechnol

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Monascus spp. are commercially important fungi due to their ability to produce beneficial secondary metabolites such as the cholesterol-lowering agent lovastatin and natural food colorants azaphilone pigments. Although hyphal branching intensively influenced the production of these secondary metabolites, the pivotal regulators of hyphal development in Monascus spp. remain unclear. To identify these important regulators, we developed an artificial intelligence (AI)–assisted image analysis tool for quantification of hyphae-branching and constructed a random T-DNA insertion library. High-throughput screening revealed that a STE kinase, MpSTE1, was considered as a key regulator of hyphal branching based on the hyphal phenotype. To further validate the role of MpSTE1, we generated an mpSTE1 gene knockout mutant, a complemented mutant, and an overexpression mutant (OE::mpSTE1). Microscopic observations revealed that overexpression of mpSTE1 led to a 63% increase in branch number while deletion of mpSTE1 reduced the hyphal branching by 68% compared to the wild-type strain. In flask cultures, the strain OE::mpSTE1 showed accelerated growth and glucose consumption. More importantly, the strain OE::mpSTE1 produced 9.2 mg/L lovastatin and 17.0 mg/L azaphilone pigments, respectively, 47.0% and 30.1% higher than those of the wild-type strain. Phosphoproteomic analysis revealed that MpSTE1 directly phosphorylated 7 downstream signal proteins involved in cell division, cytoskeletal organization, and signal transduction. To our best knowledge, MpSTE1 is reported as the first characterized regulator for tightly regulating the hyphal branching in Monascus spp. These findings significantly expanded current understanding of the signaling pathway governing the hyphal branching and development in Monascus spp. Furthermore, MpSTE1 and its analogs were demonstrated as promising targets for improving production of valuable secondary metabolites. Key points • MpSTE1 is the first characterized regulator for tightly regulating hyphal branching • Overexpression of mpSTE1 significantly improves secondary metabolite production • A high-throughput image analysis tool was developed for counting hyphal branching

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Dynamic regulation of Monascus azaphilones biosynthesis by the binary MrPigE-MrPigF oxidoreductase system

Cited by 7 publications

References 38 publications

Exploring the Subcellular Localization of Monascus Pigments Biosynthases: Preliminary Unraveling of the Compartmentalization Mechanism

Exploring the Subcellular Localization of Monascus Pigments Biosynthases: Preliminary Unraveling of the Compartmentalization Mechanism

Modular and Flexible Molecular Device for Simultaneous Cytosine and Adenine Base Editing at Random Genomic Loci in Filamentous Fungi

The serine/threonine protein kinase MpSTE1 directly governs hyphal branching in Monascus spp.

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