title: Titer improvement and pilot-scale production of platensimycin from Streptomyces platensis SB12026.
abstract: Platensimycin (PTM) and platencin (PTN), isolated from several strains of Streptomyces platensis are potent antibiotics against multi-drug resistant bacteria. PTM was also shown to have antidiabetic and antisteatotic activities in mouse models. Through a novel genome-mining method, we have recently identified six PTM and PTN dual-producing strains, and generated several mutants with improved production of PTM or PTN by inactivating the pathway-specific transcriptional repressor gene ptmR1. Among them, S. platensis SB12026 gave the highest titer of 310 mg/L for PTM. In this study, we now report titer improvement by medium and fermentation optimization and pilot-scale production and isolation of PTM from SB12026. The fermentation medium optimization was achieved by manipulating the carbon and nitrogen sources, as well as the inorganic salts. The highest titer of 1560 mg/L PTM was obtained in 15-L fermentors, using a formulated medium mainly containing soluble starch, soybean flour, morpholinepropanesulfonic acid sodium salt and CaCO3. In addition, a polyamide chromatographic step was applied to facilitate the purification and 45.14 g of PTM was successfully obtained from a 60 L scale fermentation. These results would speed up the future development of PTM as human medicine.
authors.affiliation: Xiangya International Academy of Translational Medicine, Central South University, Tongzipo Road, #172, Yuelu District, Changsha, 410013, Hunan, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Shi
authors.affiliation: Xiangya International Academy of Translational Medicine, Central South University, Tongzipo Road, #172, Yuelu District, Changsha, 410013, Hunan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Pan
authors.affiliation: Xiangya International Academy of Translational Medicine, Central South University, Tongzipo Road, #172, Yuelu District, Changsha, 410013, Hunan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Jupiter, FL, 33458, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.affiliation: Hunan Engineering Research Center of Combinatorial Biosynthesis and Natural Product Drug Discovery, Changsha, 410013, Hunan, China.
authors.forename: Songquan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Xiangya International Academy of Translational Medicine, Central South University, Tongzipo Road, #172, Yuelu District, Changsha, 410013, Hunan, China.|Hunan Engineering Research Center of Combinatorial Biosynthesis and Natural Product Drug Discovery, Changsha, 410013, Hunan, China.
authors.forename: Xiangcheng
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Jupiter, FL, 33458, USA.|Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL, 33458, USA.|Natural Products Library Initiative, The Scripps Research Institute, Jupiter, FL, 33458, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Shen
authors.affiliation: Xiangya International Academy of Translational Medicine, Central South University, Tongzipo Road, #172, Yuelu District, Changsha, 410013, Hunan, China. ywduan66@sina.com.|Hunan Engineering Research Center of Combinatorial Biosynthesis and Natural Product Drug Discovery, Changsha, 410013, Hunan, China. ywduan66@sina.com.|National Engineering Research Center of Combinatorial Biosynthesis for Drug Discovery, Changsha, 410013, Hunan, China. ywduan66@sina.com.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Xiangya International Academy of Translational Medicine, Central South University, Tongzipo Road, #172, Yuelu District, Changsha, 410013, Hunan, China. jonghuang@csu.edu.cn.|National Engineering Research Center of Combinatorial Biosynthesis for Drug Discovery, Changsha, 410013, Hunan, China. jonghuang@csu.edu.cn.
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000218:Adamantane / Q000378:metabolism*; D062365:Aminobenzoates / Q000378:metabolism*; D000627:Aminophenols / Q000378:metabolism; D000813:Anilides / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D019149:Bioreactors; D003470:Culture Media / Q000737:chemistry; D005285:Fermentation; D007218:Industrial Microbiology / Q000379:methods*; D010865:Pilot Projects; D011083:Polycyclic Compounds / Q000378:metabolism; D013302:Streptomyces / Q000145:classification / Q000378:metabolism*
chemical_list: D062365:Aminobenzoates; D000627:Aminophenols; D000813:Anilides; D000900:Anti-Bacterial Agents; D003470:Culture Media; D011083:Polycyclic Compounds; D000218:Adamantane; C510909:platensimycin; C520340:platencin
keywords: Fermentation medium optimization; Platensimycin; Polyamide chromatography; Streptomyces platensis SB12026