Centre for Synthetic Biology and the Bioeconomy

Past Seminars

Bacillus subtilis: Why does this industrial microorganism provide a valuable platform for Synthetic Biology?

Prof Colin Harwood, Centre for Bacterial Cell Biology, Institute for Cell & Molecular Biosciences, Newcastle University

Date/Time: 17th of July 2018, 13:00-14:00

Venue: CBCB Baddiley-Clark Building, large meeting room level 2

The biochemistry and physiology of Bacillus subtilis have been studied intensely for 50 years and its genomics for just over 20 years1. The initial incentive was to develop a model non-pathogenic species in which processes such as sporulation could be studies safely, but attention soon turned to this bacterium’s ability to produce important industrial enzymes (amylases and proteases). It was the demonstration of genetic transformability that provided the stimulus for most subsequent studies and B. subtilis is second only to Escherichia coli as a model bacterium. The SubtiWiki website (http://subtiwiki.uni-goettingen.de) provides detailed information on metabolic pathways, essential genes, gene expression profiles, regulons, interaction networks, etc. I will provide a short history of the key developments along a long research path leading to the importance of B. subtilis as a Synthetic Biology chassis2.

One of the most important aspects for the commercialisation of Bacillus is it ability to secret proteins into the culture medium at concentrations in excess of 20 g/L. We have developed a wide range of practical strains and tools that improve both the range and yield of proteins that can be secreted. These include the ability to self-assemble functional and tunable protein complexes in the culture medium3; a tool for locating optimal chromosomal “landing pads”4; a library of synthetic expression modules (SEMs)5 and; a collection of protease-negative strains6.

B. subtilis has also been widely used as a chassis for metabolic engineering and is used commercially for the production of vitamins such as riboflavin. A pan-European consortium mapped the expression of every gene on the chromosome under more than one hundred physiological conditions that are relevant to its live as a soil microbe and industrial bacterium7,8. In parallel, a multi-omics approach revealed the extraordinary metabolic and regulatory complexity of a single soil-living bacterial cell that more than rivals that of a single differentiated human cell.  It has also allowed us to design a series of reporters for monitoring industrial fermentations.

 

1Borriss et al., (2018) Microb. Biotechnol. 11:3-17

2Harwood et al., Meth. Microbiol. 40:119-156

3Gilbert et al., (2017). ACS Synth. Biol. 6:957-967

4Sauer et al., (2016) ASC Synth. Biol. 5:942-947

5Sauer et al., (2018) ACS Synth. Biol. In press

6Pohl et al.,  (2013) Proteomics 13:3298-3308

7Buescher et al., (2012) Science 335:1099-1103

8Nicholas et al., (2012) Science 335:1103-1106