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A case study in flux balance analysis: Lysine, a cephamycin C precursor, can also increase clavulanic acid production

Paper ID Volume ID Publish Year Pages File Format Full-Text
2705 127 2016 12 PDF Available
Title
A case study in flux balance analysis: Lysine, a cephamycin C precursor, can also increase clavulanic acid production
Abstract

•Streptomyces clavuligerus produces Cephamycin C and Clavulanic acid concomitantly.•In this paper was evaluated concomitant production of these two bioactives by FBA.•Lysine is a Cephamycin C precursor.•Lysine combined with maltose favored Clavulanic acid production.•It was possible to propose a mechanism for this behavior by means of flux analysis.

Streptomyces clavuligerus is an excellent model for studying complex relationships involved in the biosynthesis of secondary metabolites. Despite the fact that several studies have investigated the mechanisms pertaining to the biosynthesis of two bioactive compounds produced by S. clavuligerus, cephamycin C (CephC) and clavulanic acid (CA), few have focused on metabolic flux analyses of this microorganism. It was proposed a novel representative metabolic model for S. clavuligerus addressing the simultaneous production of CephC and CA using flux balance analysis methodology (FBA). Although both are synthesized via different pathway, flux analysis showed that the production of these bioactives are connected. CephC production showed high dependency on N metabolism while CA production is more related with C metabolism. Adding lysine plus maltose increased CA, an interesting outcome since lysine is a CephC precursor. Notwithstanding, it was possible to propose a mechanism for this behavior by means of flux analysis. Furthermore, the results suggest that ATP yield maximization is the objective function that best suits the conditions under investigation.

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Keywords
ACV, aminoadipyl-cysteinyl-valine tripeptide; C, carbon; CA, clavulanic acid; CAT, cadaverine aminotranferase; ccar, clavulanic acid cluster regulator; CephC, cephamycin C; FBA, flux balance analysis; KLys, monod constant for lysine for growth on lysine;
First Page Preview
A case study in flux balance analysis: Lysine, a cephamycin C precursor, can also increase clavulanic acid production
Publisher
Database: Elsevier - ScienceDirect
Journal: Biochemical Engineering Journal - Volume 112, 15 August 2016, Pages 42–53
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering