{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T07:29:10Z","timestamp":1775633350266,"version":"3.50.1"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T00:00:00Z","timestamp":1721779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,7,24]],"date-time":"2024-07-24T00:00:00Z","timestamp":1721779200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"MOST | National Key Research and Development Program of China","award":["2018YFA0900404"],"award-info":[{"award-number":["2018YFA0900404"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Appl Environ Microbiol"],"published-print":{"date-parts":[[2024,7,24]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Precursor supply plays a significant role in the production of secondary metabolites. In\n              <jats:italic>Streptomyces<\/jats:italic>\n              bacteria, propionyl-, malonyl-, and methylmalonyl-CoA are the most common precursors used for polyketide biosynthesis. Although propionyl-CoA synthetases participate in the propionate assimilation pathway and directly convert propionate into propionyl-CoA, malonyl- and methylmalonyl-CoA cannot be formed using common acyl-CoA synthetases. Therefore, both acetyl- and propionyl-CoA carboxylation, catalyzed by acyl-CoA carboxylases, should be considered when engineering a microorganism chassis to increase polyketide production. In this study, we identified a transcriptional regulator of the TetR family, BkdR, in\n              <jats:italic>Streptomyces albus<\/jats:italic>\n              B4, which binds directly to the promoter region of the neighboring\n              <jats:italic>pccAB<\/jats:italic>\n              operon. This operon encodes acetyl\/propionyl-CoA carboxylase and negatively regulates its transcription. In addition to acetate and propionate, the binding of BkdR to\n              <jats:italic>pccAB<\/jats:italic>\n              is disrupted by acetyl- and propionyl-CoA ligands. We identified a 16-nucleotide palindromic BkdR-binding motif (GTTAg\/CGGTCg\/TTAAC) in the intergenic region between\n              <jats:italic>pccAB<\/jats:italic>\n              and\n              <jats:italic>bkdR<\/jats:italic>\n              . When\n              <jats:italic>bkdR<\/jats:italic>\n              was deleted, we found an enhanced supply of malonyl- and methylmalonyl-CoA precursors in\n              <jats:italic>S. albus<\/jats:italic>\n              B4. In this study, spinosad production was detected in the recombinant strain after introducing the entire artificial biosynthesized gene cluster into\n              <jats:italic>S. albus<\/jats:italic>\n              B4. When supplemented with propionate to provide propionyl-CoA, the novel\n              <jats:italic>bkdR<\/jats:italic>\n              -deleted strain produced 29.4% more spinosad than the initial strain in trypticase soy broth (TSB) medium.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              In this study, we describe a\n              <jats:italic>pccAB<\/jats:italic>\n              operon involved in short-chain acyl-CoA carboxylation in\n              <jats:italic>S. albus<\/jats:italic>\n              B4 chassis. The TetR family regulator, BkdR, represses this operon. Our results show that BkdR regulates the precursor supply needed for heterologous spinosad biosynthesis by controlling acetyl- and propionyl-CoA assimilation. The deletion of the BkdR-encoding gene exerts an increase in heterologous spinosad yield. Our research reveals a regulatory mechanism in short-chain acyl-CoA metabolism and suggests new possibilities for\n              <jats:italic>S. albus<\/jats:italic>\n              chassis engineering to enhance heterologous polyketide yield.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aem.00838-24","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T13:10:21Z","timestamp":1718975421000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Engineering of a TetR family transcriptional regulator BkdR enhances heterologous spinosad production in\n            <i>Streptomyces albus<\/i>\n            B4 chassis"],"prefix":"10.1128","volume":"90","author":[{"given":"Wenzong","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8364-8336","authenticated-orcid":true,"given":"Hao","family":"Tang","sequence":"additional","affiliation":[{"name":"Institute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingjun","family":"Cui","sequence":"additional","affiliation":[{"name":"Institute of Engineering Biology and Health, Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, Zhejiang, 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