Computer-aided re-engineering of nonribosomal peptide and polyketide biosynthetic assembly lines
Covering: 2014 to 2019 Nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) have been the subject of engineering efforts for multiple decades. Their modular assembly line architecture potentially allows unlocking vast chemical space for biosynthesis. However, attempts thus far ar...
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| Published in | Natural product reports Vol. 36; no. 9; pp. 1249 - 1261 |
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| Main Authors | , , , |
| Format | Journal Article |
| Language | English |
| Published |
England
Royal Society of Chemistry
01.09.2019
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| Subjects | |
| Online Access | Get full text |
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| Summary: | Covering: 2014 to 2019
Nonribosomal peptide synthetases (NRPSs) and polyketide synthases (PKSs) have been the subject of engineering efforts for multiple decades. Their modular assembly line architecture potentially allows unlocking vast chemical space for biosynthesis. However, attempts thus far are often met with mixed success, due to limited molecular compatibility of the parts used for engineering. Now, new engineering strategies, increases in genomic data, and improved computational tools provide more opportunities for major progress. In this review we highlight some of the challenges and progressive strategies for the re-design of NRPSs & type I PKSs and survey useful computational tools and approaches to attain the ultimate goal of semi-automated and design-based engineering of novel peptide and polyketide products.
This review highlights recent advancements in engineering biosynthetic assembly lines and new computational tools that aid in parts search, assembly line engineering, and refinement. |
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| Bibliography: | Harald Gross is a pharmacist by training and obtained his PhD degree in 2004 from the University of Bonn, Germany, followed by 2 years of postdoctoral research at the Oregon State University in Corvallis/OR, USA and at the Scripps Institution of Oceanography in La Jolla/CA, USA. Back at the University of Bonn, he established in 2006 his own independent research group where he was mainly working on the genomics and secondary metabolism of Pseudomonas bacteria. Since 2012 he is Full Professor at the University of Tübingen. His research interests are in the field of genome-driven discovery of microbial secondary metabolites, biosynthesis research and genetic engineering. Marnix Medema is an Assistant Professor of Bioinformatics at Wageningen University, The Netherlands. In 2013, he completed his PhD in the groups of Eriko Takano and Rainer Breitling, at the University of Groningen. During his PhD he spent time in the lab of Michael Fischbach at the University of California, San Francisco, as a visiting research fellow. Following a postdoctoral fellowship in the group of Frank Oliver Glöckner at the Max Planck Institute for Marine Microbiology in Bremen, Germany, he joined Wageningen University in 2015. His group develops and applies computational tools to understand bacterial, fungal and plant natural product biosynthesis from a genomic perspective. Dr Mohammad Alanjary obtained his PhD in bioinformatics at the University of Tübingen, Germany, with a focus on antibiotic resistance. Previously he aided in the launch of the first commercial semi-conductor gene-sequencing platform and developed several procedures for performance optimization while working at IonTorrent. He is currently working at Wageningen University to develop computational methods leveraging comparative genomics for natural product discovery and engineering. Carolina Cano Prieto was born in 1984. She obtained her bachelors degree in Biology at University of Granada (Spain) followed by a MSc in Microbiology under the Spanish Educational Minister fellowship. She completed her PhD studies in 2015 under the supervision of Prof. José Antonio Salas and Dr Carlos Olano at University of Oviedo where her work was focused in identification of the polyketide biosynthesis produced by streptomycetes. Since 2016 she is a post-doctoral researcher in the lab of Prof. Dr Harald Gross at the University of Tübingen. There she currently works on the characterization and modification of NRPS biosynthetic gene clusters in Pseudomonas and Bacillus strains and with the development of biosynthetic gene clusters using synthetic biology tools. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23 |
| ISSN: | 0265-0568 1460-4752 1460-4752 |
| DOI: | 10.1039/c9np00021f |