Nature has a talent for inventing a vast number of natural products, including hybrids generated by blending different scaffolds, resulting in a myriad of bioactive chemical entities. Herein, we review the highlights and recent trends (2010–2016) in the combinatorial biosynthesis of sugar-containing antibiotics where nature's structural diversification capabilities are exploited to enable the creation of new anti-infective and anti-proliferative drugs. In this review, we describe the modern combinatorial biosynthetic approaches for polyketide synthase-derived complex and aromatic polyketides, non-ribosomal peptide synthetase-directed lipo-/glycopeptides, aminoglycosides, nucleoside antibiotics, and alkaloids, along with their therapeutic potential. Finally, we present the feasible nexus between combinatorial biosynthesis, systems biology, and synthetic biology as a toolbox to provide new antibiotics that will be indispensable in the post-antibiotic era.
Bibliographical noteFunding Information:
We thank Dr. Kris Rathwell for critical reading this manuscript. This work was supported by the National Research Foundation of Korea grant (2016R1A2A1A05005078, 2015R1A2A2A01002524 [J.W.P.]) funded by the Ministry of Science, ICT and Future Planning (MISP), the Intelligent Synthetic Biology Center of the Global Frontier Project funded by MISP (20110031961), Advanced Production Technology Development Program and High Value-added Food Technology Development Program, Ministry of Agriculture, Food and Rural Affairs, Republic of Korea. J.W.P. also thanks to the grant (PJ011066) funded by the Next-Generation BioGreen21 program, Rural Development Administration.
© 2016 Elsevier Inc.
- Anti-infective and anti-proliferative
- Combinatorial biosynthesis
- Sugar-containing antibiotics
ASJC Scopus subject areas