Systems biology is an integrated, systemic approach to the analysis and optimization of cellular processes by introducing a variety of perturbations and then measuring the system response. Altered phenotypes are created by molecular biological techniques or by altering environments. Further characterization of the phenotype leading to maximal product formation is analyzed and quantified through the use of genome-wide high-throughput omics data and genome-scale computational analysis.
Secondary metabolites are a group that includes antibiotics, pesticides, pigments, toxins, pheromones, enzyme inhibitors, immunomodulating agents, receptor antagonists and agonists, pesticides, antitumor agents, immunosuppresants, cholesterol-lowering agents, plant protectants and animal and plant growth factors—these metabolites have tremendous economic importance. This remarkable group of compounds is produced by certain restricted taxonomic groups of organisms and usually formed as mixtures of closely related members of a chemical family.
The antibiotics include β-lactams (penicillins, cephalosporins, cephamycins, clavulanic acid, and carbapenems), aminoglycosides, macrolides (erythromycin, oleandomycin, pikromycin, tylosin and amphotericin B), and polyenes.
Metabolic engineering has been used to replace the normal promoter to increase antibiotic production many-fold. High-level expression of positive regulatory genes has led to major increases in antibiotic production.
The production of antibiotics in heterologous hosts via combinatorial biosynthesis is becoming popular in antibiotic production and discovery. Over 200 new polyketides have been made by combinatorial biosynthesis, which also has been used to construct macrolides with new sugar moieties.
An important new strategy to improve the discovery of new antibiotics is genome mining, which has come about due to advances in microbial genomics. Mining of whole-genome sequences and genome scanning allows the rapid identification of more than 450 clusters of genes (in antibiotic-producing cultures) that encode the biosynthesis of new bioactive products. Genome mining also allows one to predict structure based on gene sequences.
Research in this area includes mining of whole-genome sequences, genome scanning, and heterologous expression. The discovery of novel chemistry has also been a result. Genomics could provide a huge group of new targets against which natural products can be screened.
Biopharmaceutical products, a key part of the pharmaceutical industry, are biotechnology’s major contribution. These products can be categorized into four major groups: protein therapeutics with enzymatic activity (e.g., insulin), protein vaccines, protein therapeutics with special targeting activity (e.g., monoclonal antibodies) and protein diagnostics (e.g., biomarkers).
Biologics accounted for over $80 billion in sales in 2008. Six of these therapeutic proteins were among the best-selling drugs in the U.S. in that year. Monoclonal antibodies and Fc-fusion proteins made up 43% of this market value. The market reached over $90 billion in 2010.