Metabolic flux phenotyping of secondary metabolism in cyanobacteria

• Published in: Trends in microbiology (Regular ed.) 2023-11, Vol.31 (11), p.1118-1130
• Main Authors: Babele, Piyoosh K., Srivastava, Amit, Young, Jamey D.
• Format: Article
• Language: English
• Subjects: genome-scale metabolic models; metabolic flux analysis; secondary metabolism; secondary metabolites; systems metabolic engineering
• ISSN: 0966-842X; 1878-4380
• DOI: 10.1016/j.tim.2023.05.005

Metabolic flux analysis (MFA) of photoautotrophic metabolism requires dynamic 13CO2 labeling experiments and isotopically nonstationary MFA (INST-MFA).Systems metabolic engineering (SME) is an efficient approach for improving bioproduction in cyanobacteria.Combinations of 13C- and 15N-labeled tracers can be used to gain better insight into the carbon and nitrogen metabolism of cyanobacteria within a single experiment.The redox state of cyanobacteria should be considered when manipulating their metabolic networks.With metabolomics-assisted MFA, the flux distribution at key metabolic nodes in intermediary metabolism can be examined, identifying flux to wasteful pathways. Cyanobacteria generate energy from photosynthesis and produce various secondary metabolites with diverse commercial and pharmaceutical applications. Unique metabolic and regulatory pathways in cyanobacteria present new challenges for researchers to enhance their product yields, titers, and rates. Therefore, further advancements are critically needed to establish cyanobacteria as a preferred bioproduction platform. Metabolic flux analysis (MFA) quantitatively determines the intracellular flows of carbon within complex biochemical networks, which elucidate the control of metabolic pathways by transcriptional, translational, and allosteric regulatory mechanisms. The emerging field of systems metabolic engineering (SME) involves the use of MFA and other omics technologies to guide the rational development of microbial production strains. This review highlights the potential of MFA and SME to optimize the production of cyanobacterial secondary metabolites and discusses the technical challenges that lie ahead.