scholarly journals Using Chemobiosynthesis and Synthetic Mini-Polyketide Synthases To Produce Pharmaceutical Intermediates in Escherichia coli

2010 ◽  
Vol 76 (15) ◽  
pp. 5221-5227 ◽  
Author(s):  
Hugo G. Menzella ◽  
John R. Carney ◽  
Yong Li ◽  
Daniel V. Santi

ABSTRACT Recombinant microbial whole-cell biocatalysis is a valuable approach for producing enantiomerically pure intermediates for the synthesis of complex molecules. Here, we describe a method to produce polyketide intermediates possessing multiple stereogenic centers by combining chemobiosynthesis and engineered mini-polyketide synthases (PKSs). Chemobiosynthesis allows the introduction of unnatural moieties, while a library of synthetic bimodular PKSs expressed from codon-optimized genes permits the introduction of a variety of ketide units. To validate the approach, intermediates for the synthesis of trans-9,10-dehydroepothilone D were generated. The designer molecules obtained have the potential to greatly reduce the manufacturing cost of epothilone analogues, thus facilitating their commercial development as therapeutic agents.

2018 ◽  
Vol 24 (8) ◽  
pp. 904-910 ◽  
Author(s):  
Yidan Gao ◽  
Hengtong Fang ◽  
Lu Fang ◽  
Dawei Liu ◽  
Jinsong Liu ◽  
...  

The antimicrobial peptides (AMPs) are a group of unique naturally occurring anti-microbial compounds with around 50 amino acids. It represents promising therapeutic agents to the infectious disease without concerning about drug resistance. However, commercial development of these peptides for even the simplest application has been hindered by the limitations of sources, instability, toxicity and bioavailability. To improve the properties of the artificial synthesized AMPs, the modification and design are the hotspots of the AMPs research. In fact, more than half of the known AMPs are naturally modified. In this review, two types of modification strategies, biochemical modification and chemical modification were summarized. Although, the chemical modification is versatile and direct, the manufacturing cost is greatly increased compared to the antibiotics. With the recent progress of the protein modification enzyme, the biochemical modification of the antimicrobial peptide followed by heterologous expression has great application prospects.


2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Weichao Ma ◽  
Weijia Cao ◽  
Bowen Zhang ◽  
Kequan Chen ◽  
Quanzhen Liu ◽  
...  

2013 ◽  
Vol 12 (1) ◽  
pp. 103 ◽  
Author(s):  
Yongjin J Zhou ◽  
Wei Yang ◽  
Lei Wang ◽  
Zhiwei Zhu ◽  
Sufang Zhang ◽  
...  

2013 ◽  
Vol 79 (11) ◽  
pp. 3516-3521 ◽  
Author(s):  
Ramesh Prasad Pandey ◽  
Tai Feng Li ◽  
Eun-Hee Kim ◽  
Tokutaro Yamaguchi ◽  
Yong Il Park ◽  
...  

ABSTRACTA UDP-glycosyltransferase fromBacillus licheniformiswas exploited for the glycosylation of phloretin. Thein vitroglycosylation reaction confirmed the production of five phloretin glucosides, including three novel glucosides. Consequently, we demonstrated the application of the same glycosyltransferase for the efficient whole-cell biocatalysis of phloretin in engineeredEscherichia coli.


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