Biotechnology and Bioprocess Engineering 2023; 28(6): 990-1004  
Pan-genome Analysis Reveals Comparative Genomic Features of Central Metabolic Pathways in Methylorubrum extorquens
Gyu Min Lee, Zoe K. Scott-Nevros, Sang-Mok Lee, and Donghyuk Kim
Gyu Min Lee, Zoe K. Scott-Nevros, Sang-Mok Lee, Donghyuk Kim
School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea
Donghyuk Kim*
School of Life Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea
Tel: +82-52-217-2945; Fax: +82-52-217-3009
E-mail: dkim@unist.ac.kr
Received: May 23, 2022; Revised: June 29, 2022; Accepted: July 23, 2022; Published online: December 31, 2023.
© The Korean Society for Biotechnology and Bioengineering. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Methylobacterium is a genus belonging to the pink-pigmented facultative methylotrophs, which can use C1 substrates as a sole carbon source. Methylorubrum extorquens (formerly Methylobacterium extorquens) is a potentially valuable bacteria in methanol-based bioindustry producing high-value-added chemicals. Thus, it is critical to understand the core metabolic pathways of M. extorquens strains for further advancement as a platform bacterium in the bioindustry. However, there are no reported systems biological approaches comparing different M. extorquens strains. This paper focuses on comparing the genomic properties of seven completely sequenced M. extorquens strains, including M. extorquens PA1, which was resequenced, and M. extorquens ATCC 55366, which was newly sequenced in this study. Pan-genome analysis indicated that a total of 10,431 ortholog clusters composed the pan-genome of these M. extorquens strains, including 3,507 core genome, 1,860 accessory genome, and 5,064 unique genome clusters. The functional annotation discovered that genes related to signal transduction were the most abundant in the pan-genome. Pan-genome analysis of two different habitat-specific groups revealed that the strains isolated from various soil environments had a higher percentage of genes involved in mobilome in their core genome. Subsequent exploration for secondary metabolite biosynthesis clusters denoted the unique ability of M. extorquens AM1 to produce various toblerols. M. extorquens PA1 could be a strong candidate for industrial strain development because of its minimal genome size with fully conserved central metabolism. This study provides the first inclusive insight into the differences in genomic characteristics of central metabolic networks of M. extorquens.
Keywords: Methylorubrum extorquens, methylotrophy, pan-genome, comparative genomics, carbon metabolic pathways, industrial strain development

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