Heterologous Production of the C33-C45 Polyketide Fragment of Anticancer Apratoxins in a Cyanobacterial Host

被引:2
|
作者
Dhakal, Dipesh [1 ,2 ]
Kallifidas, Dimitris [1 ,2 ]
Chen, Manyun [1 ,2 ]
Kokkaliari, Sofia [1 ,2 ]
Chen, Qi-Yin [1 ,2 ]
Paul, Valerie J. [3 ]
Ding, Yousong [1 ,2 ]
Luesch, Hendrik [1 ,2 ]
机构
[1] Univ Florida, Dept Med Chem, Gainesville, FL 32610 USA
[2] Univ Florida, Ctr Nat Prod Drug Discovery & Dev CNPD3, Gainesville, FL 32610 USA
[3] Smithsonian Marine Stn, Ft Pierce, FL 34949 USA
基金
美国国家卫生研究院;
关键词
BIOLOGICAL EVALUATION; EXPRESSION; POTENT;
D O I
10.1021/acs.orglett.3c00462
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
A polyketide synthase subcluster of cytotoxic apratoxin A was isolated from a Moorena bouillonii environmental DNA library and engineered with a thioesterase II domain for heterologous expression in the filamentous cyanobacterium Anabaena sp. PCC7120. Further engineering with a rhamnose-inducible promoter led to the production of (2R,3R,5R,7R)-3,7-dihydroxy-2,5,8,8-tetrame-thylnonanoic acid, a stereogenically rich chiral building block that is important to the efficient synthesis of apratoxin analogues, representing the first synthetic biology attempt for this type of polyketide fragment.
引用
收藏
页码:2238 / 2242
页数:5
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