Progressive strain development of industrially relevant microbes via genome editing and systems biology

Abstract

Microorganisms underpin modern industrial biotechnology; however, wild-type strains frequently exhibit suboptimal metabolic flux distribution, regulatory constraints, and limited product titers. To address these limitations, strain improvement strategies have evolved from classical mutagenesis and recombination approaches to precision genome-scale engineering. Recombinant DNA methodologies, including protoplast fusion, transduction, and conjugation, combined with advanced CRISPR-based systems (Cas9, Cas12, base editing, and prime editing), now enable programmable, locus-specific genomic modification with high fidelity. The integration of multi-omics platforms (genomics, epigenomics, transcriptomics, proteomics, metabolomics, and regulomics) with single-cell sequencing, fluxomics, and constraint-based metabolic modeling has transformed strain engineering into a predictive and systems-driven discipline. These approaches facilitate the rational rewiring of metabolic pathways, flux balancing, and regulatory circuits to enhance productivity and robustness. This review examines the progression from conventional strain improvement to genome-scale design strategies and evaluates methodologies for optimizing bacterial and fungal cell factories. It further discusses industrial translation, scalability constraints, and emerging opportunities for developing resilient microbial platforms for sustainable and carbon-efficient biomanufacturing.

Keywords

Genome editing / Systems biology / CRISPR/Cas9 / Omics / Green products / Energy efficiency

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Funding

National Science Foundation(2314099)

Anusandhan National Research Foundation (ANRF)(SRG/2021/001243)

Research and Development Cell, Lovely Professional University, India(LPU/DRD/SEED/SAC/090922/25274)

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