Directed natural product biosynthesis gene cluster capture and expression in the model bacterium Bacillus subtilis

Yongxin Li, Zhongrui Li, Kazuya Yamanaka, Ying Xu, Weipeng Zhang, Hera Vlamakis, Roberto Kolter, Bradley S. Moore, Pei-Yuan Qian

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90 Scopus citations


Bacilli are ubiquitous low G+C environmental Gram-positive bacteria that produce a wide assortment of specialized small molecules. Although their natural product biosynthetic potential is high, robust molecular tools to support the heterologous expression of large biosynthetic gene clusters in Bacillus hosts are rare. Herein we adapt transformation-associated recombination (TAR) in yeast to design a single genomic capture and expression vector for antibiotic production in Bacillus subtilis. After validating this direct cloning plug-and-playa approach with surfactin, we genetically interrogated amicoumacin biosynthetic gene cluster from the marine isolate Bacillus subtilis 1779. Its heterologous expression allowed us to explore an unusual maturation process involving the N-acyl-asparagine pro-drug intermediates preamicoumacins, which are hydrolyzed by the asparagine-specific peptidase into the active component amicoumacin A. This work represents the first direct cloning based heterologous expression of natural products in the model organism B. subtilis and paves the way to the development of future genome mining efforts in this genus.
Original languageEnglish (US)
JournalScientific Reports
Issue number1
StatePublished - Mar 24 2015
Externally publishedYes

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledged KAUST grant number(s): SA-C0040, UK-C0016
Acknowledgements: This study was generously supported by a grant (DY125-15-T-02) from China Ocean Mineral Resources Research and Development Association, award SA-C0040/UK-C0016 from the King Abdullah University of Science and Technology to P.Y.Q., and funding from the NIH (R01-GM085770) to B.S.M.
This publication acknowledges KAUST support, but has no KAUST affiliated authors.


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