Bacillus subtilis: a universal cell factory for industry, agriculture, biomaterials and medicine

Su, Y., Liu, C., Fang, H., & Zhang, D. (2020). Bacillus subtilis: a universal cell factory for industry, agriculture, biomaterials and medicine. Microbial Cell Factories, 19, 173. https://doi.org/10.1186/s12934-020-01436-8

What This Review Covers

This group of scientists compiled a review to show why Bacillus subtilis is often chosen when industry needs a microbe to make something valuable. It is safe, fast-growing, and dependable. The article covers wide-reaching applications—like producing vitamins, digestive enzymes, and biomedical materials—and explains that certain bacteria can be cultivated much like crops, but instead of yielding food, they yield ingredients that go into supplements, medicines, and agricultural products. That versatility and practicality are what make B. subtilis the subject of study for these authors.

Su and colleagues describe Bacillus subtilis as a “universal cell factory” and organize the review around three main themes:

1. The toolkit that allows researchers to adjust the microbe,
2. The secretion pathways that send products out of the cell, and
3. The wide range of applications already in use.

Why Bacillus subtilis is valued as a cell factory

• Practical growth: It completes fermentation in ~48 hours (compared to ~180 hours for Saccharomyces cerevisiae) and can use low-cost substrates.
• Safe status: Many strains are “generally recognized as safe” (GRAS), which makes them acceptable for food, feed, and supplement production.
• Natural secretion: Unlike some microbes, B. subtilis pushes proteins out of the cell, simplifying recovery and reducing bottlenecks.

Tools for adjusting how the microbe works

The review doesn’t expect readers to follow every molecular detail, but it emphasizes that B. subtilis has a mature set of tools that let scientists make small, precise adjustments:

• Genome editing: Modern CRISPR-based systems allow quick and accurate changes to improve yield or remove unwanted byproducts.
• Expression tuning: Promoter libraries and other genetic “switches” let scientists turn enzyme production up or down, similar to adjusting a dimmer knob.
• Integration strategies: Improved systems make sure changes are stable and consistently expressed across batches.

How products move out of the cell

B. subtilis is unusual for how efficiently it exports finished products into the surrounding medium. The review outlines three main routes:

• Sec pathway: The default system for sending proteins out in an unfolded state, where they finish folding afterward.
• Tat pathway: A channel for already folded proteins marked with a special signal sequence.
• ABC transporters: Membrane pumps that move particular substrates directly across the cell wall.

What Bacillus subtilis is already making

• Vitamins and small molecules: Industrial production of riboflavin (B2) and menaquinone-7 (K2/MK-7); successful strain development for N-acetylglucosamine (GlcNAc) and hyaluronic acid with controlled titers and molecular weights.
• Enzymes: Large-scale secretion of amylases, proteases, cellulases, and xylanases—critical for food, feed, and industrial uses.
• Biomaterials and medicine: Engineered biofilms that can act as living materials, and durable spores that serve as carriers for enzymes or antigens.
• Agriculture and probiotics: B. subtilis spores survive processing, germinate in the gut, and release enzymes that support nutrient absorption and pathogen control.