Development of Streptomyces sp. FR-008 as an emerging chassis  

作　　者：Qian Liu Liping Xiao Yuanjie Zhou Kunhua Deng Gaoyi Tan Yichao Han Xinhua Liu Zixin Deng Tiangang Liu 

机构地区：[1]State Key Laboratory of Microbial Metabolism and School of Life Science&Biotechnology,Shanghai Jiao Tong University,Shanghai 200240,China [2]Key Laboratory of Combinatorial Biosynthesis and Drug Discovery,Ministry of Education,Wuhan University School of Pharmaceutical Sciences,Wuhan 430071,China [3]Hubei Engineering Laboratory for Synthetic Microbiology,Wuhan Institute of Biotechnology,Wuhan 430075,China [4]J1 Biotech,Co.Ltd.,Wuhan 430075,China

出　　处：《Synthetic and Systems Biotechnology》2016年第3期207-214,共8页合成和系统生物技术（英文）

基　　金：grants from J1 Biotech Co.Ltd.,the 973 Project(2011CBA00800,2012CB721000);the 863 Project(2012AA02A701);the Ministry of Science and Technology of China,and from the Natural Science Foundation of Hubei Province(2015CFB415).

摘　　要：Microbial-derived natural products are important in both the pharmaceutical industry and academic research.As the metabolic potential of original producer especially Streptomyces is often limited by slow growth rate,complicated cultivation profile,and unfeasible genetic manipulation,so exploring a Streptomyces as a super industrial chassis is valuable and urgent.Streptomyces sp.FR-008 is a fast-growing microorganism and can also produce a considerable amount of macrolide candicidin via modular polyketide synthase.In this study,we evaluated Streptomyces sp.FR-008 as a potential industrial-production chassis.First,PacBio sequencing and transcriptome analyses indicated that the Streptomyces sp.FR-008 genome size is 7.26 Mb,which represents one of the smallest of currently sequenced Streptomyces genomes.In addition,we simplified the conjugation procedure without heat-shock and pre-germination treatments but with high conjugation efficiency,suggesting it is inherently capable of accepting heterologous DNA.In addition,a series of promoters selected from literatures was assessed based on GusA activity in Streptomyces sp.FR-008.Compared with the common used promoter ermE*-p,the strength of these promoters comprise a library with a constitutive range of 60e860%,thus providing the useful regulatory elements for future genetic engineering purpose.In order to minimum the genome,we also target deleted three endogenous polyketide synthase(PKS)gene clusters to generate a mutant LQ3.LQ3 is thus an“updated”version of Streptomyces sp.FR-008,producing fewer secondary metabolites profiles than Streptomyces sp.FR-008.We believe this work could facilitate further development of Streptomyces sp.FR-008 for use in biotechnological applications.

关 键 词：smallest URGENT GERMINATION 

分 类 号：Q93[生物学—微生物学]