Engineering Bio-based Monomers for Materials from Unusual Microbes
Anaerobic fungi (A) are early-branching eukaryotes found in large herbivores that are extremely difficult to grow at scale. However, recently our laboratory discovered that anaerobic fungi produce a wealth of small molecules like baumin (B), which is a polyketide that contains many of the targeted chemistries for polymers (vinyl (blue), alcohol and ester (red) groups which can be utilized in orthogonal polymerizations) as well as high degrees of asymmetry and chirality (green). Several sequenced strains of anaerobic fungi (C) are untapped sources of small molecule monomers for next-generation functional materials, as they encode an array of biosynthetic genes like polyketide synthases (PKS) and non-ribosomal peptide synthases (NRPS).
Synthetic biology has delivered a host of tools to refactor model microorganisms for biomanufacturing, yet the diversity of chemicals that can be produced at scale is limited to low-complexity products like fuels. However, microorganisms synthesize a vast array of small molecules and peptides called natural products, which are untapped building blocks to make materials with novel functional properties of use to the DoD. The overall goal of this project is to accelerate the production of next-generation biomaterials relevant to the DoD, which are sourced from a unique set of biosynthetic genes recently identified in anaerobic gut fungi.
This project pursues an interdisciplinary approach that applies synthetic biology principles to unusual organisms to produce extremely complex natural products at scale for the first time. These high-complexity natural products serve as bio-derived material building blocks (monomers, chain end units, initiators) that are chiral, asymmetric, and feature reactive functional groups (exchangeable bonds, hydrogen bonding capability) that are unique and inaccessible via conventional synthetic routes. Since most natural products are made at extremely low levels by cells, we will focus on developing high-throughput genetic tools to amplify biosynthetic gene production in microbes, which will also enable novel natural products to be identified and linked to their respective biosynthetic pathway. In this effort we will benefit from high-throughput culture and analysis instrumentation enabled by our recently awarded Synthetic Biology Robotic Platform, which provides unparalleled infrastructure for cultivation optimization, and purification/analysis of target monomers. Novel bio-derived monomers will be structurally characterized and used in homopolymerizations, copolymerizations or to modify existing materials leading to thermoplastic and thermoset polymer resins with improved and/or new performance. Key biosynthetic genes of interest are those that make polyketides and non-ribosomal peptides, which build compounds that feature the chirality, reactive functional groups, asymmetry, etc. that is so desirable in bio-based monomers. This research will open the way for a range of complex monomers and next-generation materials of use to the DoD that can be produced biologically.
