Development of eco-friendly bioplastics using microbes​

[Background & Objectives]

Because some microbes produce bio-vinyl monomers possessing both complicate structures and radical polymerizability, they are able to be utilized as novel building blocks of polymers (Ref., Appl. Microbiol. Biotechnol., 104(21) 9041 (2020)). However, the monomers which have been found so far are few in number and the technology for production of these monomers is not developed yet. Furthermore, the biosynthetic mechanisms of almost all these monomers are still unknown. More recently, it has been reported that itaconic acid, a bio-vinyl monomer produced by a fungus Aspergillus terreus, and its polymerized materials show anti-inflammatory and anti-tumor activities, respectively, suggesting that they would be useful as a seed compound and medical polymers having these bioactivities. The aims of study are to develop screening and production methods for bio-vinyl monomers and to create novel medical polymers having bioactivities such as anti-inflammatory and anti-tumor activities, following to reveal these bioactivities of the monomers.

[Research]

We have developed a screen method called "DISCOVER (Direct Screening based on Coupling Reactions for Vinyl Compound Producers)" for the bio-vinyl monomers based on two-step coupling reactions, thiol-ene and Heck reactions, with terminal double bonds of the monomers. We are now categorizing the bio-vinyl monomers discovered so far and developing the technology for production of these monomers (Ref., Sci. Reports, 9(1) 16007 (2019)). Using the screening method DISCOVER, some novel fungi producing bio-vinyl monomers have been isolated and subsequently these structures have been identified using MS and NMR analyses. Bioactivity assays of the monomers revealed that some of which show anti-tumor activity. We are synthesizing polymeric substances consisting of these monomers and then evaluating these bioactivities. A bacterium Escherichia coli has been genetically modified to produce itaconic acid. Based on metabolic engineering, expression of cis-aconitate decarboxylase gene (cad) and aconitase gene (acnB) and inactivation of isocitrate lyase gene (icd) have been demonstrated, leading to itaconic acid production. This would open the way to produce bio-vinyl monomers heterologously (Ref., J. Gen. Appl. Microbiol., 60(5) 191 (2014); J. Biosci. Bioeng., 119(5) 548 (2015); J. Biotechnol., 195 43 (2015)).​

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[Applications & Future works]

Compared to vinyl monomers produced from petroleum, bio-vinyl monomers possess higher number of carbon (more than C5), heteroatoms such as oxygen and nitrogen. Therefore, we can create new types of polymers having distinctive mechanical properties and bioactivities. Metabolic engineering would design the biosynthetic pathways of bio-vinyl monomers and it would enable to produce these monomers using heterologous hosts such as E. coli. Bio-vinyl monomers would be useful as not only building blocks and also seed compounds for drug design. Bio-vinyl innovation would make it possible a new paradigm based on bio-vinyl monomers.