Titer improvement and pilot-scale production of platensimycin from Streptomyces platensis SB12026

被引：28

作者：

Shi, Jun ^{[1
]}

Pan, Jian ^{[1
]}

Liu, Ling ^{[1
]}

Yang, Dong ^{[4
]}

Lu, Songquan ^{[2
]}

Zhu, Xiangcheng ^{[1
,2
]}

Shen, Ben ^{[4
,5
,6
]}

Duan, Yanwen ^{[1
,2
,3
]}

Huang, Yong ^{[1
,3
]}

机构：

[1] Cent S Univ, Xiangya Int Acad Translat Med, Tongzipo Rd 172, Changsha 410013, Hunan, Peoples R China

[2] Hunan Engn Res Ctr Combinatorial Biosynth & Nat P, Changsha 410013, Hunan, Peoples R China

[3] Natl Engn Res Ctr Combinatorial Biosynth Drug Dis, Changsha 410013, Hunan, Peoples R China

[4] Scripps Res Inst, Dept Chem, Jupiter, FL 33458 USA

[5] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA

[6] Scripps Res Inst, Nat Prod Lib Initiat, Jupiter, FL 33458 USA

来源：

JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY | 2016年 / 43卷 / 07期

基金：

美国国家卫生研究院;

关键词：

Platensimycin; Fermentation medium optimization; Polyamide chromatography; Streptomyces platensis SB12026; DEFINED MEDIUM; INHIBITOR; ANTIBIOTICS; FABF;

D O I：

10.1007/s10295-016-1769-z

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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 anti-steatotic 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.

引用

页码：1027 / 1035

页数：9