Biosynthesis of ilamycins featuring unusual building blocks and engineered production of enhanced anti-tuberculosis agents

Junying Ma (), Hongbo Huang, Yunchang Xie, Zhiyong Liu, Jin Zhao, Chunyan Zhang, Yanxi Jia, Yun Zhang, Hua Zhang, Tianyu Zhang and Jianhua Ju ()
Additional contact information
Junying Ma: South China Sea Institute of Oceanology, Chinese Academy of Sciences
Hongbo Huang: South China Sea Institute of Oceanology, Chinese Academy of Sciences
Yunchang Xie: South China Sea Institute of Oceanology, Chinese Academy of Sciences
Zhiyong Liu: Chinese Academy of Sciences
Jin Zhao: Institute of Laboratory Medicine, Guangdong Medical University
Chunyan Zhang: South China Sea Institute of Oceanology, Chinese Academy of Sciences
Yanxi Jia: South China Sea Institute of Oceanology, Chinese Academy of Sciences
Yun Zhang: South China Sea Institute of Oceanology, Chinese Academy of Sciences
Hua Zhang: Institute of Laboratory Medicine, Guangdong Medical University
Tianyu Zhang: Chinese Academy of Sciences
Jianhua Ju: South China Sea Institute of Oceanology, Chinese Academy of Sciences

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: Abstract Tuberculosis remains one of the world’s deadliest communicable diseases, novel anti-tuberculosis agents are urgently needed due to severe drug resistance and the co-epidemic of tuberculosis/human immunodeficiency virus. Here, we show the isolation of six anti-mycobacterial ilamycin congeners (1–6) bearing rare L-3-nitro-tyrosine and L-2-amino-4-hexenoic acid structural units from the deep sea-derived Streptomyces atratus SCSIO ZH16. The biosynthesis of the rare L-3-nitrotyrosine and L-2-amino-4-hexenoic acid units as well as three pre-tailoring and two post-tailoring steps are probed in the ilamycin biosynthetic machinery through a series of gene inactivation, precursor chemical complementation, isotope-labeled precursor feeding experiments, as well as structural elucidation of three intermediates (6–8) from the respective mutants. Most impressively, ilamycins E1/E2, which are produced in high titers by a genetically engineered mutant strain, show very potent anti-tuberculosis activity with an minimum inhibitory concentration value ≈9.8 nM to Mycobacterium tuberculosis H37Rv constituting extremely potent and exciting anti-tuberculosis drug leads.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-00419-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00419-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-00419-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().