Biomanufacturing: history and perspective.

Biomanufacturing is a type of manufacturing that utilizes biological systems (e.g., living microorganisms, resting cells, animal cells, plant cells, tissues, enzymes, or in vitro synthetic (enzymatic) systems) to produce commercially important biomolecules for use in the agricultural, food, material, energy, and pharmaceutical industries. History of biomanufacturing could be classified into the three revolutions in terms of respective product types (mainly), production platforms, and research technologies. Biomanufacturing 1.0 focuses on the production of primary metabolites (e.g., butanol, acetone, ethanol, citric acid) by using mono-culture fermentation; biomanufacturing 2.0 focuses on the production of secondary metabolites (e.g., penicillin, streptomycin) by using a dedicated mutant and aerobic submerged liquid fermentation; and biomanufacturing 3.0 focuses on the production of large-size biomolecules-proteins and enzymes (e.g., erythropoietin, insulin, growth hormone, amylase, DNA polymerase) by using recombinant DNA technology and advanced cell culture. Biomanufacturing 4.0 could focus on new products, for example, human tissues or cells made by regenerative medicine, artificial starch made by in vitro synthetic biosystems, isobutanol fermented by metabolic engineering, and synthetic biology-driven microorganisms, as well as exiting products produced by far better approaches. Biomanufacturing 4.0 would help address some of the most important challenges of humankind, such as food security, energy security and sustainability, water crisis, climate change, health issues, and conflict related to the energy, food, and water nexus.