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      Insight into the phylogeny and metabolic divergence of Monascus species ( M. pilosus, M. ruber, and M. purpureus) at the genome level

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          Abstract

          Background

          Species of the genus Monascus are economically important and widely used in the production of food colorants and monacolin K. However, they have also been known to produce the mycotoxin citrinin. Currently, taxonomic knowledge of this species at the genome level is insufficient.

          Methods

          This study presents genomic similarity analyses through the analysis of the average nucleic acid identity of the genomic sequence and the whole genome alignment. Subsequently, the study constructed a pangenome of Monascus by reannotating all the genomes and identifying a total of 9,539 orthologous gene families. Two phylogenetic trees were constructed based on 4,589 single copy orthologous protein sequences and all the 5,565 orthologous proteins, respectively. In addition, carbohydrate active enzymes, secretome, allergic proteins, as well as secondary metabolite gene clusters were compared among the included 15 Monascus strains.

          Results

          The results clearly revealed a high homology between M. pilosus and M. ruber, and their distant relationship with M. purpureus. Accordingly, all the included 15 Monascus strains should be classified into two distinctly evolutionary clades, namely the M. purpureus clade and the M. pilosus- M. ruber clade. Moreover, gene ontology enrichment showed that the M. pilosus- M. ruber clade had more orthologous genes involved with environmental adaptation than the M. purpureus clade. Compared to Aspergillus oryzae, all the Monascus species had a substantial gene loss of carbohydrate active enzymes. Potential allergenic and fungal virulence factor proteins were also found in the secretome of Monascus. Furthermore, this study identified the pigment synthesis gene clusters present in all included genomes, but with multiple nonessential genes inserted in the gene cluster of M. pilosus and M. ruber compared to M. purpureus. The citrinin gene cluster was found to be intact and highly conserved only among M. purpureus genomes. The monacolin K gene cluster was found only in the genomes of M. pilosus and M. ruber, but the sequence was more conserved in M. ruber.

          Conclusion

          This study provides a paradigm for phylogenetic analysis of the genus Monascus, and it is believed that this report will lead to a better understanding of these food microorganisms in terms of classification, metabolic differentiation, and safety.

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          Most cited references77

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          Cytoscape: a software environment for integrated models of biomolecular interaction networks.

          Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
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            MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets.

            We present the latest version of the Molecular Evolutionary Genetics Analysis (Mega) software, which contains many sophisticated methods and tools for phylogenomics and phylomedicine. In this major upgrade, Mega has been optimized for use on 64-bit computing systems for analyzing larger datasets. Researchers can now explore and analyze tens of thousands of sequences in Mega The new version also provides an advanced wizard for building timetrees and includes a new functionality to automatically predict gene duplication events in gene family trees. The 64-bit Mega is made available in two interfaces: graphical and command line. The graphical user interface (GUI) is a native Microsoft Windows application that can also be used on Mac OS X. The command line Mega is available as native applications for Windows, Linux, and Mac OS X. They are intended for use in high-throughput and scripted analysis. Both versions are available from www.megasoftware.net free of charge.
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              RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies

              Motivation: Phylogenies are increasingly used in all fields of medical and biological research. Moreover, because of the next-generation sequencing revolution, datasets used for conducting phylogenetic analyses grow at an unprecedented pace. RAxML (Randomized Axelerated Maximum Likelihood) is a popular program for phylogenetic analyses of large datasets under maximum likelihood. Since the last RAxML paper in 2006, it has been continuously maintained and extended to accommodate the increasingly growing input datasets and to serve the needs of the user community. Results: I present some of the most notable new features and extensions of RAxML, such as a substantial extension of substitution models and supported data types, the introduction of SSE3, AVX and AVX2 vector intrinsics, techniques for reducing the memory requirements of the code and a plethora of operations for conducting post-analyses on sets of trees. In addition, an up-to-date 50-page user manual covering all new RAxML options is available. Availability and implementation: The code is available under GNU GPL at https://github.com/stamatak/standard-RAxML. Contact: alexandros.stamatakis@h-its.org Supplementary information: Supplementary data are available at Bioinformatics online.
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                Author and article information

                Contributors
                Journal
                Front Microbiol
                Front Microbiol
                Front. Microbiol.
                Frontiers in Microbiology
                Frontiers Media S.A.
                1664-302X
                25 May 2023
                2023
                : 14
                : 1199144
                Affiliations
                [1] 1State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology , Tianjin, China
                [2] 2State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology, Ministry of Education , Tianjin, China
                [3] 3Biodesign Center, Key Laboratory of Engineering Biology for Low-Carbon Manufacturing, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences , Tianjin, China
                [4] 4Haihe Laboratory of Synthetic Biology , Tianjin, China
                Author notes

                Edited by: Helianthous Verma, University of Delhi, India

                Reviewed by: Paulina Corral, University of Seville, Spain; Utkarsh Sood, University of Delhi, India

                *Correspondence: Huanhuan Liu, lh_tust@ 123456tust.edu.cn
                Article
                10.3389/fmicb.2023.1199144
                10249731
                37303795
                f780003c-efa6-4e0e-9d94-b012d1567e86
                Copyright © 2023 Zhang, Cui, Chen, Li, Mao, Mao, Li, Guo, Wang, Liao and Liu.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 03 April 2023
                : 09 May 2023
                Page count
                Figures: 8, Tables: 2, Equations: 0, References: 77, Pages: 15, Words: 9819
                Funding
                This research was supported by the National Key Research and Development Program of China (No. 2020YFA0908300), Tianjin Synthetic Biotechnology Innovation Capacity Improvement Projects (TSBICIP-PTJS-001, TSBICIP-PTJJ-007, and TSBICIP-KJGG-006), Innovation Fund of Haihe Laboratory of Synthetic Biology (No. 22HHSWSS00021), and the National Natural Science Foundation of China (No. 31800072).
                Categories
                Microbiology
                Original Research
                Custom metadata
                Evolutionary and Genomic Microbiology

                Microbiology & Virology
                monascus,phylogenetic analysis,taxonomic divergence,secondary metabolite gene clusters,pan-genome

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