fulltext.study @t Gmail

Enhancement of tacrolimus productivity in Streptomyces tsukubaensis by the use of novel precursors for biosynthesis

Paper ID Volume ID Publish Year Pages File Format Full-Text
17194 42650 2012 8 PDF Available
Title
Enhancement of tacrolimus productivity in Streptomyces tsukubaensis by the use of novel precursors for biosynthesis
Abstract

In this report the optimization of biosynthesis of tacrolimus, the immunosupressant widely used in transplantology and dermatology was described. The enhancement of the productivity of Streptomyces tsukubaensis strain was achieved by development of new precursors of tacrolimus biosynthesis, which should allow to reduce the costs of the process.The enrichment of the fermentation medium in pyridine-2-carboxylic acid (picolinic acid), piperidine-2-carboxylic acid (pipecolic acid), pyridine-3-carboxylic acid (nicotinic acid) or pyridine-3-carboxylic acid amide (nicotinamide) caused significant growth of the productivity of tacrolimus: 7-fold, 6-fold, 3-fold and 5-fold, respectively. The optimum concentration of the precursors in medium was 0.0025–0.005%. The investigation of the kinetics of tacrolimus biosynthesis together with the analysis of the impact of tested compounds on the culture growth and NAD (nicotinamide adenine dinucleotide) concentration in S. tsukubaensis cells enables to put forward a hypothesis concerning the mechanism of action of tested culture medium additives. The compounds active as tacrolimus precursors (pipecolic and picolinic acids) are more effective than these active mainly as the growth promoters (nicotinamide and nicotinic acid). Nicotinamide and nicotinic acid – vitamin B3 components – promote S. tsukubaensis growth most probably due to the stimulation of NAD/NADP biosynthesis.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► We enhanced productivity of immunosuppressant tacrolimus 7-fold in Streptomyces sp. ► We tested piperidine- and pyridine-derivatives as the cultivation medium supplements. ► The mechanism of action of the tested medium supplements was proposed. ► Proposed optimization of the medium will reduce the costs of the drug biosynthesis.

Keywords
Tacrolimus; Streptomyces tsukubaensis; NAD; Piperidine carboxylic acid; Vitamin B3
First Page Preview
Enhancement of tacrolimus productivity in Streptomyces tsukubaensis by the use of novel precursors for biosynthesis
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us
Publisher
Database: Elsevier - ScienceDirect
Journal: Enzyme and Microbial Technology - Volume 51, Issues 6–7, 10 December 2012, Pages 388–395
Authors
, , , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us