Research Article: NAD+-dependent HDAC inhibitor stimulates Monascus pigment production but inhibit citrinin

Date Published: August 23, 2017

Publisher: Springer Berlin Heidelberg

Author(s): Yan Hu, Youxiang Zhou, Zejing Mao, Huihui Li, Fusheng Chen, Yanchun Shao.


Monascus species are edible fungi due to the production of food colorant and other beneficial compounds. Hence, it has been an attractive thesis to improve their productivities. Increasing numbers of investigations revealed that regulating the activities of histone deacetylases can significantly perturb secondary metabolites (SM) production at a global level. In this study, dihydrocoumarin (DHC, an inhibitor of the Sirtuin family of NAD+-dependent deacetylases) was used to treat Monascus ruber for evaluating its effects on organism growth and SM production. The results revealed that the variation trends of colonial sizes, biomass and mycotoxin were in a dose-dependent manner. Generally, they decreased with the increased DHC concentrations in the designed range. But the variation trend of pigment was different. Comparison of SM profile, three new peaks occurred to the mycelia extractions from DHC-treated strain corresponding to molecular weights 402, 416 and 444, respectively. These three compounds were identified as Monasfluol B, Monascus azaphilone C and acetyl-monasfluol B (a new Monascus chemical pigment structure). In short, DHC can stimulate M. ruber strain to produce more pigment-like polyketides but inhibition of mycotoxin (citrinin).

Partial Text

Filamentous fungi are important sources of secondary metabolites (SM) which can produce antibiotics, organic acid, immunosuppressants, siderophores, antitumor agents and toxins (Brakhage 2013). Monascus species are very important microbial resources in oriental countries due to their abilities to produce food additives and pharmaceutical ingredients, such as edible pigments, natural antioxidant dimerumic acid, anti-hyper-cholesterolemic agent monacolins, hypotensive agent gamma-amino butyric acid (GABA) as well as sterol and isoflavones. Hence, it has been an attractive thesis to improve their productivities. Bioinformatics analysis revealed that the genome of Monascus strains contained more gene backbones encoding SMs than currently characterized compounds (Chen et al. 2015), suggesting Monascus strains have great potential to produce new compounds.

In recent years, researchers adopted diverse approaches to improve bioactive compounds or discover new compounds for industrial application. A series of investigations proved that acetylation modification plays an important role in regulating SM production via modification of HDACs activities (Albright et al. 2015). In this study, DHC has multiple effects on SM production of M. ruber. Firstly, suitable range of DHC can improve pigment yields but reduce mycotoxin (citrinin). More importantly, new pigment-like polyketide was discovered. So DHC is an alternative agent to stimulate M. ruber to produce much more pigment-like compounds.




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