Abstract
Lincomycin A is a clinically important antibiotic produced by Streptomyces lincolnensis that is used against gram-positive bacteria. To increase the yield of lincomycin A, a calcium gluconate feeding strategy was studied in a 15 L bioreactor. The results showed that the addition time of calcium gluconate was optimal during the late fermentation process to ensure a higher yield of lincomycin A. The optimum addition was continuous feeding at a speed of 0.0638 g/L/h from 111 to 158 h, which can increase the lincomycin A titer to 9160 mg/L, 41.3% higher than that without gluconate feeding. Enzyme activities of the central metabolic pathways, accumulation of intermediate metabolites, NADPH and NADH concentrations, and NADPH/NADH ratio were determined to investigate the mechanism of enhanced lincomycin A production by calcium gluconate addition. The activities of key enzymes of the pentose phosphate pathway (PPP) (glucose 6-phosphate dehydrogenase) and TCA cycle (isocitrate dehydrogenase) were enhanced by approximately twofold. A higher ratio of NADPH/NADH was observed in the fermentation process with the optimized feeding strategy providing sufficient reducing power. These data indicated that more flux flows through the PPP and the TCA cycle to provide more precursors, ATP and reducing power to support the synthesis of lincomycin A. The results showed a new strategy to improve the production of lincomycin A by manipulating the flux through the PPP and the TCA cycle.
Highlights
Produced by Streptomyces lincolnensis, lincomycin is a clinically important lincosamide antibiotic with potent activity against gram-positive bacteria (Mason and Dietz1964; Koberska et al 2008)
The results showed a new strategy to improve the production of lincomycin A by manipulating the flux through the phosphate pathway (PPP) and the Keywords: Streptomyces lincolnensis, Lincomycin, Calcium gluconate, NADPH/NADH ratio
The condensation of MTL and PPL is unusual in that two bacterial thiols play constructive role in the biosynthesis of lincomycin A: thiol ergothioneine (EGT) acts as a carrier to template the assembly of GDP-activated MTL and PPL moiety, and thiol mycothiol (MSH) is the sulfur donor for lincomycin maturation through two unusual S-glycosylation (Zhao et al 2015; Zhang et al 2018)
Summary
Produced by Streptomyces lincolnensis, lincomycin is a clinically important lincosamide antibiotic with potent activity against gram-positive bacteria (Mason and Dietz1964; Koberska et al 2008). Produced by Streptomyces lincolnensis, lincomycin is a clinically important lincosamide antibiotic with potent activity against gram-positive bacteria 25% of the antibacterial activity of lincomycin A (Kucers et al 1997). The condensation of MTL and PPL is unusual in that two bacterial thiols play constructive role in the biosynthesis of lincomycin A: thiol ergothioneine (EGT) acts as a carrier to template the assembly of GDP-activated MTL and PPL moiety, and thiol mycothiol (MSH) is the sulfur donor for lincomycin maturation through two unusual S-glycosylation (Zhao et al 2015; Zhang et al 2018). MTL is generated via a transaldol reaction catalyzed by LmbR to form GDP-d-αd-octose as the key intermediate in the MTL biosynthetic pathway (Sasaki et al 2012; Lin et al 2014).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
