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Because of that, BCAA catabolism needs fine tuning of flux balances for enhancing the production of polyketide antibiotics. To enhance BCAA catabolism for pikromycin production in Streptomyces venezuelae ATCC 15439, three key enzymes of BCAA catabolism, 3-ketoacyl acyl carrier protein synthase III, acyl-CoA dehydrogenase, and branched chain \u03b1-keto acid dehydrogenase (BCDH) were manipulated. BCDH overexpression in the wild type strain resulted in 1.3 fold increase in pikromycin production compared to that of WT, resulting in total 25\u00a0mg\/L of pikromycin. To further increase pikromycin production, methylmalonyl-CoA mutase linked to succinyl-CoA production was overexpressed along with BCDH. Overexpression of the two enzymes resulted in the highest titer of total macrolide production of 43\u00a0mg\/L, which was about 2.2 fold increase compared to that of the WT. However, it accumulated and produced dehydroxylated forms of pikromycin and methymycin, including their derivatives as well. It indicated that activities of pikC, P450 monooxygenase, newly became a bottleneck in pikromycin synthesis.<\/jats:p>","DOI":"10.1007\/s10295-018-2024-6","type":"journal-article","created":{"date-parts":[[2018,3,10]],"date-time":"2018-03-10T01:03:58Z","timestamp":1520643838000},"page":"293-303","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Production of pikromycin using branched chain amino acid catabolism in <i>Streptomyces venezuelae<\/i> ATCC 15439"],"prefix":"10.1093","volume":"45","author":[{"given":"Jeong Sang","family":"Yi","sequence":"first","affiliation":[{"name":"0000 0004 0470 5905 grid.31501.36 School of Chemical and Biological Engineering Seoul National University 1, Gwanak-ro, Gwanak-gu 08826 Seoul Republic of Korea"},{"name":"0000 0004 0470 5905 grid.31501.36 Institute of Molecular Biology and Genetics Seoul National University 08826 Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minsuk","family":"Kim","sequence":"additional","affiliation":[{"name":"0000 0004 0470 5905 grid.31501.36 Institute of Engineering Research Seoul National University 08826 Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun-Jung","family":"Kim","sequence":"additional","affiliation":[{"name":"0000 0004 0470 5905 grid.31501.36 Institute of Molecular Biology and Genetics Seoul National University 08826 Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung-Gee","family":"Kim","sequence":"additional","affiliation":[{"name":"0000 0004 0470 5905 grid.31501.36 School of Chemical and Biological Engineering Seoul National University 1, Gwanak-ro, Gwanak-gu 08826 Seoul Republic of Korea"},{"name":"0000 0004 0470 5905 grid.31501.36 Institute of Molecular Biology and Genetics Seoul National University 08826 Seoul Republic of Korea"},{"name":"0000 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