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From Biosynthesis to Functional Biomaterials

The Schmidt-Dannert laboratory currently pursues two major focus areas: 1. Characteriztion and design of genetically programmable protein-based nanomaterials for biocatalysis and as functional materials, and 2. Harnessing the unique biosynthetic and redox biocatalytic machineries of higher fungiunique biosynthetic and redox biocatalytic machineries of higher fungi.

Microbes and plants synthesize a tremendous diversity of chemical compounds that is unmatched by chemical synthetic methods. Biological systems use enzymes with different functions as catalysts to achieve the synthesis of complex molecules at room temperature and in the absence of organic solvents. We are interested in exploring and utilizing the enzymatic manchineries of biological systems to enable the sustainable production of valuable chemicals recombinant microbes and in cell-free biocatalytic systems. 

Self-organization at the nano- to macro scale is a key characteristic of all biological systems. Inspired by natures ingenuity and the prospects offered by exploring biomolecular self-assembly mechanisms, we arre interested in characterizing and designing new types of genetically programmables self-assembling protein-based nanoarchitectures for a wide range of applications in biocatalysis, biosynthesis, and for the fabrication of new types of bio(inorganic)-nanomaterials


Genetically programmable, self-assembling protein-nanomaterials

 


In biological systems, proteins, nucleic acids and lipids are precisely organized to form higher ordered structures. Principles underlying the assembly and organization of natural bionanomaterials can be harnessed for the design and fabrication of robust materials for biocatalysis and as functional biomaterials with emergent properties. Self-assembly provides a low-cost approach for bottom-up construction of supramolecular biomaterials from simple building blocks. Principles underlying these processes have inspired the design of self-assembling biomaterials across multiple scales for a different of applications. By varying building block composition, molecular structures and environmental conditions, assemblies can be controlled and altered by changing interaction types and strengths.

Peptides and proteins offer the most versatility for the assembly of such designed structures due to the chemical diversity of their amino acid components. Unlike nucleic acid-based structures, protein materials are highly robust and can be readily modified and tailored for desired applications. Importantly, materials built from protein building blocks are genetically encoded. As such, they are programmable and can be produced recombinantly at low cost. Self-assembly and patterning also underlie the formation of a wide range of biocomposite materials made by living organisms for e.g. mechanical stability, protection and defense. Many of these materials have extraordinary properties. For example, they combine lightweight with light refraction, toughness, strength and elasticity which are properties that cannot be easily replicated synthetically but would be of enormous interest for the fabrication of bioinspired materials.

We are designing and characterizing different types of self-organizing protein nanomaterials. In ongoing project, we are investigating and designing self-assembling scaffolds for multi-enzyme biocatalysis, fabrication of living and self-healing materials, and by interfacing protein-based nanomaterials with biomineralization mechanisms, the design of novel biocomposite materials.


Natural Products and Enzymes from Fungi


Mushrooms (Basidiomycota) have been used for centuries in traditional medicine, and they are known to produce a range of unique chemicals, many of them with demonstrated antimicrobial, cytotoxic, immune-modulating and anti-inflammatory activities. Yet, the biosynthetic pathways that make these molecules in this group of fungi are largely unknown. We are identifying and characterizing the biosynthesis of novel compounds in this fascinating class of organisms. Over the past several years, we have investigated the biosynthesis of isoprenoid natural products in mushrooms. These compounds represent the largest class of natural products and are the major class of bioactive molecules made by mushrooms. We have identified and characterized the biosynthesis of one group of pharmaceutically important isoprenoids - the sesquiterpenes - in several mushroom species, which led to the development of a predictive, bioinformatic framework for this class of compounds.

In ongoing research, we are taking advantage of our expertise with this class of fungi by building a unique Field-to-Laboratory Biobank of Midwestern mushrooms that we are screening for the discovery of novel bioactive natural products. Mushrooms have also evolved the unique ability to degrade recalcitrant lignocellulose, ending the carboniferous period by allowing recycling of carbon bound in the lignin of dead plant material. They have become masters of oxidative biocatalysis performed by novel and expanded families of many different types of oxidoreductase enzymes. These types of enzymes are of great utility for the biomanufacturing of chemicals. We are therefore searching our mushroom strain collection for enzymes with new activities that we can use to synthesize desired chemicals. Our goal is the creation of a biocatalyst toolkit that will enhance our bioproduction capabilities.