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Identification of the Actinomycin D Biosynthetic Pathway from Marine-Derived Streptomyces costaricanus SCSIO ZS0073
Liu, Mengchan1; Jia, Yanxi1; Xie, Yunchang; Zhang, Chunyan1; Ma, Junying; Sun, Changli; Ju, Jianhua1
2019
Source PublicationMARINE DRUGS
ISSN1660-3397
Volume17Issue:4Pages:240
AbstractBioactive secondary metabolites from Streptomycetes are important sources of lead compounds in current drug development. Streptomyces costaricanus SCSIO ZS0073, a mangrove-derived actinomycete, produces actinomycin D, a clinically used therapeutic for Wilm's tumor of the kidney, trophoblastic tumors and rhabdomyosarcoma. In this work, we identified the actinomycin biosynthetic gene cluster (BGC) acn by detailed analyses of the S. costaricanus SCSIO ZS0073 genome. This organism produces actinomycin D with a titer of similar to 69.8 g mL(-1) along with traces of actinomycin X-o. The acn cluster localized to a 39.8 kb length region consisting of 25 open reading frames (ORFs), including a set of four genes that drive the construction of the 4-methyl-3-hydroxy-anthranilic acid (4-MHA) precursor and three non-ribosomal peptide synthetases (NRPSs) that generate the 4-MHA pentapeptide semi-lactone, which, upon dimerization, affords final actinomycin D. Furthermore, the acn cluster contains four positive regulatory genes acnWU4RO, which were identified by in vivo gene inactivation studies. Our data provide insights into the genetic characteristics of this new mangrove-derived actinomycin D bioproducer, enabling future metabolic engineering campaigns to improve both titers and the structural diversities possible for actinomycin D and related analogues.
DepartmentLMB
Keywordactinomycin D biosynthetic gene cluster biosynthesis bioproducer Streptomyces costaricanus
DOI10.3390/md17040240
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Document Type期刊论文
Identifierhttp://ir.scsio.ac.cn/handle/344004/17867
Collection中科院海洋生物资源可持续利用重点实验室
Affiliation1.Chinese Acad Sci, CAS Key Lab Trop Marine Bioresources & Ecol, Guangdong Key Lab Marine Mat Med, South China Sea Inst Oceanol, 164 West Xingang Rd, Guangzhou 510301, Guangdong, Peoples R China
2.Univ Chinese Acad Sci, Coll Oceanog, Beijing 100049, Peoples R China
Recommended Citation
GB/T 7714
Liu, Mengchan,Jia, Yanxi,Xie, Yunchang,et al. Identification of the Actinomycin D Biosynthetic Pathway from Marine-Derived Streptomyces costaricanus SCSIO ZS0073[J]. MARINE DRUGS,2019,17(4):240.
APA Liu, Mengchan.,Jia, Yanxi.,Xie, Yunchang.,Zhang, Chunyan.,Ma, Junying.,...&Ju, Jianhua.(2019).Identification of the Actinomycin D Biosynthetic Pathway from Marine-Derived Streptomyces costaricanus SCSIO ZS0073.MARINE DRUGS,17(4),240.
MLA Liu, Mengchan,et al."Identification of the Actinomycin D Biosynthetic Pathway from Marine-Derived Streptomyces costaricanus SCSIO ZS0073".MARINE DRUGS 17.4(2019):240.
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