Divergence of metabolites in three phylogenetically close Monascus species ( M. pilosus , M. ruber, and M. purpureus ) b

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RESEARCH ARTICLE

Open Access

Divergence of metabolites in three phylogenetically close Monascus species (M. pilosus, M. ruber, and M. purpureus) based on secondary metabolite biosynthetic gene clusters Yuki Higa1, Young-Soo Kim1, Md. Altaf-Ul-Amin2, Ming Huang2, Naoaki Ono3,2*

and Shigehiko Kanaya2,3

Abstract Background: Species of the genus Monascus are considered to be economically important and have been widely used in the production of yellow and red food colorants. In particular, three Monascus species, namely, M. pilosus, M. purpureus, and M. ruber, are used for food fermentation in the cuisine of East Asian countries such as China, Japan, and Korea. These species have also been utilized in the production of various kinds of natural pigments. However, there is a paucity of information on the genomes and secondary metabolites of these strains. Here, we report the genomic analysis and secondary metabolites produced by M. pilosus NBRC4520, M. purpureus NBRC4478 and M. ruber NBRC4483, which are NBRC standard strains. We believe that this report will lead to a better understanding of red yeast rice food. Results: We examined the diversity of secondary metabolite production in three Monascus species (M. pilosus, M. purpureus, and M. ruber) at both the metabolome level by LCMS analysis and at the genome level. Specifically, M. pilosus NBRC4520, M. purpureus NBRC4478 and M. ruber NBRC4483 strains were used in this study. Illumina MiSeq 300 bp paired-end sequencing generated 17 million high-quality short reads in each species, corresponding to 200 times the genome size. We measured the pigments and their related metabolites using LCMS analysis. The colors in the liquid media corresponding to the pigments and their related metabolites produced by the three species were very different from each other. The gene clusters for secondary metabolite biosynthesis of the three Monascus species also diverged, confirming that M. pilosus and M. purpureus are chemotaxonomically different. M. ruber has similar biosynthetic and secondary metabolite gene clusters to M. pilosus. The comparison of secondary metabolites produced also revealed divergence in the three species. (Continued on next page)

* Correspondence: [email protected] 3 Data Science Center, Nara Institute of Science and Technology, Ikoma-shi, Takayama-cho, Nara 8916-5, Japan 2 Graduate School of Science and Technology, Nara Institute of Science and Technology, Ikoma-shi, Takayama-cho, Nara 8916-5, Japan Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless i