Abstract:
:Antimycins are a family of natural products generated from a hybrid nonribosomal peptide synthetase (NRPS)-polyketide synthase (PKS) assembly line. Although they possess an array of useful biological activities, their structural complexity makes chemical synthesis challenging, and their biosynthesis has thus far been dependent on slow-growing source organisms. Here, we reconstituted the biosynthesis of antimycins in Escherichia coli, a versatile host that is robust and easy to manipulate genetically. Along with Streptomyces genetic studies, the heterologous expression of different combinations of ant genes enabled us to systematically confirm the functions of the modification enzymes, AntHIJKL and AntO, in the biosynthesis of the 3-formamidosalicylate pharmacophore of antimycins. Our E. coli-based antimycin production system can not only be used to engineer the increased production of these bioactive compounds, but it also paves the way for the facile generation of novel and diverse antimycin analogues through combinatorial biosynthesis.
journal_name
ACS Synth Bioljournal_title
ACS synthetic biologyauthors
Liu J,Zhu X,Seipke RF,Zhang Wdoi
10.1021/sb5003136subject
Has Abstractpub_date
2015-05-15 00:00:00pages
559-65issue
5issn
2161-5063journal_volume
4pub_type
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journal_title:ACS synthetic biology
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journal_title:ACS synthetic biology
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