{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T11:52:02Z","timestamp":1782906722844,"version":"3.54.5"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,10,23]],"date-time":"2024-10-23T00:00:00Z","timestamp":1729641600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000199","name":"U.S. Department of Agriculture","doi-asserted-by":"crossref","award":["WIS04018"],"award-info":[{"award-number":["WIS04018"]}],"id":[{"id":"10.13039\/100000199","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Dairy Innovation Hub","award":["AAK5475"],"award-info":[{"award-number":["AAK5475"]}]},{"name":"Dairy Business Innovation Alliance"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2024,10,23]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Bioconversion of abundant lactose-replete whey permeate to value-added chemicals holds promise for valorization of this expanding food processing waste. Efficient conversion of whey permeate-borne lactose requires adroit microbial engineering to direct carbon to the desired chemical. An engineered strain of\n              <jats:italic>Clostridium beijerinckii<\/jats:italic>\n              NCIMB 8052 (\n              <jats:italic>C. beijerinckii<\/jats:italic>\n              _mgsA+mgR) that produces 87% more butanol on lactose than the control strain was assessed for global transcriptomic changes. The results revealed broadly contrasting gene expression patterns in\n              <jats:italic>C. beijerinckii<\/jats:italic>\n              _mgsA+mgR relative to the control strain. These were characterized by widespread decreases in the abundance of mRNAs of Fe-S proteins in\n              <jats:italic>C. beijerinckii<\/jats:italic>\n              _mgsA+mgR, coupled with increased differential expression of lactose uptake and catabolic genes, iron uptake genes, two-component signal transduction and motility genes, and genes involved in the biosynthesis of vitamins B\n              <jats:sub>5<\/jats:sub>\n              and B\n              <jats:sub>12<\/jats:sub>\n              , aromatic amino acids (particularly tryptophan), arginine, and pyrimidines. Conversely, the mRNA patterns suggest that the L-aspartate-dependent\n              <jats:italic>de novo<\/jats:italic>\n              biosynthesis of NAD as well as biosynthesis of lysine and asparagine and metabolism of glycine and threonine were likely down-regulated. Furthermore, genes involved in cysteine and methionine biosynthesis and metabolism, including cysteine desulfurase\u2014a central player in Fe-S cluster biosynthesis\u2014equally showed reductions in mRNA abundance. Genes involved in biosynthesis of capsular polysaccharides and stress response also showed reduced mRNA abundance in\n              <jats:italic>C. beijerinckii<\/jats:italic>\n              _mgsA+mgR. The results suggest that remodeling of cellular and metabolic networks in\n              <jats:italic>C. beijerinckii<\/jats:italic>\n              _mgsA+mgR to counter anticipated effects of methylglyoxal production from heterologous expression of methylglyoxal synthase led to enhanced growth and butanol production in\n              <jats:italic>C. beijerinckii<\/jats:italic>\n              _mgsA+mgR.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Biological production of commodity chemicals from abundant waste streams such as whey permeate represents an opportunity for decarbonizing chemical production. Whey permeate remains a vastly underutilized feedstock for bioproduction purposes. Thus, enhanced understanding of the cellular and metabolic repertoires of lactose-mediated production of chemicals such as butanol promises to identify new targets that can be fine tuned in recombinant and native microbial strains to engender stronger coupling of whey permeate-borne lactose to value-added chemicals. Our results highlight new genetic targets for future engineering of\n              <jats:italic>C. beijerinckii<\/jats:italic>\n              for improved butanol production on lactose and ultimately in whey permeate.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aem.01012-24","type":"journal-article","created":{"date-parts":[[2024,9,11]],"date-time":"2024-09-11T13:00:45Z","timestamp":1726059645000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Transcriptomic characterization of recombinant\n            <i>Clostridium beijerinckii<\/i>\n            NCIMB 8052 expressing methylglyoxal synthase and glyoxal reductase from\n            <i>Clostridium pasteurianum<\/i>\n            ATCC 6013"],"prefix":"10.1128","volume":"90","author":[{"given":"Santosh","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Agyeman-Duah","sequence":"additional","affiliation":[{"name":"Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian M.","family":"Awaga-Cromwell","sequence":"additional","affiliation":[{"name":"Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5518-6530","authenticated-orcid":true,"given":"Victor C.","family":"Ujor","sequence":"additional","affiliation":[{"name":"Department of Food Science, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.3168\/jds.S0022-0302(79)83389-5"},{"key":"e_1_3_4_3_2","unstructured":"OECD-FAO (Organization for Economic Co-operation and Development Food and Agriculture Organization of the United Nations). 2014. 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