Characterization of Regulatory and Transporter Genes in the Biosynthesis of Anti-Tuberculosis Ilamycins and Production in a Heterologous Host

Marine Drugs - Tập 18 Số 4 - Trang 216
Jianqiao He1,2, Wei Xin1,2, Zhijie Yang1,2, Yan Li1, Jianhua Ju1,3,2, Junying Ma1,3
1CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Guangdong Key Laboratory of Marine Materia Medica, RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou, 510301, China
2University of Chinese Academy of Sciences, Beijing, 100049, China
3Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory, Guangzhou 510301, China

Tóm tắt

Ilamycins are cyclopeptides with novel structures that have been isolated from different Actinomycetes. They showed strong anti-tuberculosis activity and could serve as important anti-tuberculosis drug leads. The functions of the pre-tailoring and the post-tailoring genes in the biosynthesis of ilamycins have been elucidated, but the functions of the regulatory and transporter genes remain elusive. We reported herein the functions of four genes in ilamycin biosynthetic gene cluster (ila BGC) including two regulatory genes (ilaA and ilaB) and two transporter genes (ilaJ and ilaK) and the heterologous expression of ila BGC. The IlaA and IlaB were unambiguously shown to be negative and positive regulator of ilamycins biosynthesis, respectively. Consistent with these roles, inactivation of ilaA and ilaB (independent of each other) was shown to enhance and abolish the production of ilamycins, respectively. Total yields of ilamycins were enhanced 3.0-fold and 1.9-fold by inactivation of ilaA and overexpression of ilaB compared to those of in the Streptomyces atratus SCSIO ZH16, respectively. In addition, the ila BGC was successfully expressed in Streptomyces coelicolor M1152, which indicated that all biosynthetic elements for the construction of ilamycins were included in the PAC7A6. These results not only lay a foundation for further exploration of ilamycins, but also provide the genetic elements for synthetic biology.

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Marine Drugs

Tập 18 Số 4

216

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