Knowledge extraction from literature and enzyme sequences complements FBA analysis in metabolic engineering

Abstract

Flux balance analysis (FBA) using genome-scale metabolic model (GSM) is a useful method for improving the bio-production of useful compounds. However, FBA often does not impose important constraints such as nutrients uptakes, by-products excretions and gases (oxygen and carbon dioxide) transfers. Furthermore, important information on metabolic engineering such as enzyme amounts, activities, and characteristics caused by gene expression and enzyme sequences is basically not included in GSM. Therefore, simple FBA is often not sufficient to search for metabolic manipulation strategies that are useful for improving the production of target compounds. In this study, we proposed a method using literature and enzyme search to complement the FBA-based metabolic manipulation strategies. As a case study, this method was applied to shikimic acid production by Corynebacterium glutamicum to verify its usefulness. As unique strategies in literature-mining, overexpression of the transcriptional regulator SugR and gene disruption related to by-products productions were complemented. In the search for alternative enzyme sequences, it was suggested that those candidates are searched for from various species based on features captured by deep learning, which are not simply homologous to amino acid sequences of the base enzymes.

Improving Gibberellin GA3 Production with the Construction of a Genome-Scale Metabolic Model of Fusarium fujikuroi

“…The initial application of GSMMs in Haemophilus influenza allowed for the prediction of cell phenotypes through integrative analysis of bioinformatic data . Subsequently, GSMMs have been developed and applied to various microorganisms, including Escherichia coli (model ec_ i ML1515), Limosilactobacillus reuteri (model i TN656), Corynebacterium glutamicum ( i CW773), and many others. Notably, high-quality GEM for nonmodel industrial microorganisms has been established, such as Zymomonas mobiles (model i ZM516), Mortierella alpina (model i CY1106), and A.…”