An efficient microbial-based method for production of high-purity Monascus azaphilones pigments

Duan, Yali; Jia, Lili; Pei, Xiaolin; Wei, Xuetuan; Li, Mu

doi:10.1016/j.lwt.2022.114053

Cited by 3 publications

(2 citation statements)

References 33 publications

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“…Extraction and quantification of lovastatin and azaphilone was performed as we previously described (Duan et al 2022b , 2023 ). After 10 days of cultivation, M. purpureus mycelia were disrupted by high-pressure homogenization using a French press.…”

Section: Methodsmentioning

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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Section: Methodsmentioning

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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“…However, the biological mechanism underlying this recognition is unclear. 44 Isolation and Identification of Monaspins A and B. M. purpureus and A. oryzae produced abundant secondary metabolites, such as azaphilone, kojic acid, citrinin and Monacolin K, 45,46 which hampered the isolation of Monaspins A and B. The entire purification procedure began by separating and removing azaphilones using a two-phase system with different pH value.…”

Section: Screening For the Pair Strain With M Purpureus Through Bioin...mentioning

confidence: 99%

Monaspin B, a Novel Cyclohexyl-furan from Cocultivation of Monascus purpureus and Aspergillus oryzae, Exhibits Potent Antileukemic Activity

Meng,

Tan,

Duan

et al. 2024

J. Agric. Food Chem.

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Natural products are a rich resource for the discovery of innovative drugs. Microbial cocultivation enables discovery of novel natural products through tandem enzymatic catalysis between different fungi. In this study, Monascus purpureus, as a food fermentation strain capable of producing abundant natural products, was chosen as an example of a cocultivation pair strain. Cocultivation screening revealed that M. purpureus and Aspergillus oryzae led to the production of two novel cyclohexyl-furans, Monaspins A and B. Optimization of the cocultivation mode and media enhanced the production of Monaspins A and B to 1.2 and 0.8 mg/L, respectively. Monaspins A and B were structurally elucidated by HR-ESI-MS and NMR. Furthermore, Monaspin B displayed potent antiproliferative activity against the leukemic HL-60 cell line by inducing apoptosis, with a half-maximal inhibitory concentration (IC 50 ) of 160 nM. Moreover, in a mouse leukemia model, Monaspin B exhibited a promising in vivo antileukemic effect by reducing white blood cell, lymphocyte, and neutrophil counts. Collectively, these results indicate that Monaspin B is a promising candidate agent for leukemia therapy.

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Improved natural food colorant production in the filamentous fungus Monascus ruber using CRISPR-based engineering

Yoon

Han

Shin

et al. 2023

Food Research International

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An efficient microbial-based method for production of high-purity Monascus azaphilones pigments

Cited by 3 publications

References 33 publications

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

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

Monaspin B, a Novel Cyclohexyl-furan from Cocultivation of Monascus purpureus and Aspergillus oryzae, Exhibits Potent Antileukemic Activity

Improved natural food colorant production in the filamentous fungus Monascus ruber using CRISPR-based engineering

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