{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T05:55:55Z","timestamp":1774072555011,"version":"3.50.1"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"Supplement_2","license":[{"start":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T00:00:00Z","timestamp":1609372800000},"content-version":"vor","delay-in-days":30,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001863","name":"New Energy and Industrial Technology Development Organization","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001863","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Exploring metabolic pathways is one of the key techniques for developing highly productive microbes for the bioproduction of chemical compounds. To explore feasible pathways, not only examining a combination of well-known enzymatic reactions but also finding potential enzymatic reactions that can catalyze the desired structural changes are necessary. To achieve this, most conventional techniques use manually predefined-reaction rules, however, they cannot sufficiently find potential reactions because the conventional rules cannot comprehensively express structural changes before and after enzymatic reactions. Evaluating the feasibility of the explored pathways is another challenge because there is no way to validate the reaction possibility of unknown enzymatic reactions by these rules. Therefore, a technique for comprehensively capturing the structural changes in enzymatic reactions and a technique for evaluating the pathway feasibility are still necessary to explore feasible metabolic pathways.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We developed a feasible-pathway-exploration technique using chemical latent space obtained from a deep generative model for compound structures. With this technique, an enzymatic reaction is regarded as a difference vector between the main substrate and the main product in chemical latent space acquired from the generative model. Features of the enzymatic reaction are embedded into the fixed-dimensional vector, and it is possible to express structural changes of enzymatic reactions comprehensively. The technique also involves differential-evolution-based reaction selection to design feasible candidate pathways and pathway scoring using neural-network-based reaction-possibility prediction. The proposed technique was applied to the non-registered pathways relevant to the production of 2-butanone, and successfully explored feasible pathways that include such reactions.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaa809","type":"journal-article","created":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T11:11:42Z","timestamp":1599649902000},"page":"i770-i778","source":"Crossref","is-referenced-by-count":10,"title":["Feasible-metabolic-pathway-exploration technique using chemical latent space"],"prefix":"10.1093","volume":"36","author":[{"given":"Taiki","family":"Fuji","sequence":"first","affiliation":[{"name":"Center for Exploratory Research, Research and Development Group , Kokubunji-shi, Tokyo 185-8601, Japan"},{"name":", Hitachi, Ltd. , Kokubunji-shi, Tokyo 185-8601, Japan"}]},{"given":"Shiori","family":"Nakazawa","sequence":"additional","affiliation":[{"name":"Center for Exploratory Research, Research and Development Group , Kokubunji-shi, Tokyo 185-8601, Japan"},{"name":", Hitachi, Ltd. , Kokubunji-shi, Tokyo 185-8601, Japan"}]},{"given":"Kiyoto","family":"Ito","sequence":"additional","affiliation":[{"name":"Center for Exploratory Research, Research and Development Group , Kokubunji-shi, Tokyo 185-8601, Japan"},{"name":", Hitachi, Ltd. , Kokubunji-shi, Tokyo 185-8601, Japan"}]}],"member":"286","published-online":{"date-parts":[[2020,12,29]]},"reference":[{"key":"2024030713585511100_btaa809-B1","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1093\/bioinformatics\/btu750","article-title":"M-path: a compass for navigating potential metabolic pathways","volume":"31","author":"Araki","year":"2014","journal-title":"Bioinformatics"},{"key":"2024030713585511100_btaa809-B2","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/0893-6080(94)90046-9","article-title":"Democracy in neural nets: voting schemes for classification","volume":"7","author":"Battiti","year":"1994","journal-title":"Neural Networks"},{"key":"2024030713585511100_btaa809-B3","doi-asserted-by":"crossref","first-page":"D633","DOI":"10.1093\/nar\/gkx935","article-title":"The MetaCyc database of metabolic pathways and enzymes","volume":"46","author":"Caspi","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2024030713585511100_btaa809-B4","doi-asserted-by":"crossref","first-page":"e0140508","DOI":"10.1371\/journal.pone.0140508","article-title":"Metabolic engineering of klebsiella pneumoniae for the production of 2-butanone from glucose","volume":"10","author":"Chen","year":"2015","journal-title":"PLoS One"},{"key":"2024030713585511100_btaa809-B5","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1016\/j.tibtech.2019.01.003","article-title":"Systems metabolic engineering strategies: integrating systems and synthetic biology with metabolic engineering","volume":"37","author":"Choi","year":"2019","journal-title":"Trends Biotechnol"},{"issue":"Suppl. 1","key":"2024030713585511100_btaa809-B6","doi-asserted-by":"crossref","first-page":"D344","DOI":"10.1093\/nar\/gkm791","article-title":"Chebi: a database and ontology for chemical entities of biological interest","volume":"36","author":"Degtyarenko","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"2024030713585511100_btaa809-B7","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.ymben.2017.12.002","article-title":"Retropath2. 0: a retrosynthesis workflow for metabolic engineers","volume":"45","author":"Del\u00e9pine","year":"2018","journal-title":"Metabolic Eng"},{"key":"2024030713585511100_btaa809-B8","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1021\/acscentsci.7b00572","article-title":"Automatic chemical design using a data-driven continuous representation of molecules","volume":"4","author":"G\u00f3mez-Bombarelli","year":"2018","journal-title":"ACS Cent. 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