Ben Shen

Ben Shen

BTI Ben Shen

Ben Shen

Scripps

Website
Leveraging a large microbial strain collection for natural products studies

Scripps Florida houses one of the world’s largest actinobacterial strain collections, totaling >125,00 strains. These strains were isolated over the last eight decades and from 69 different countries, spanning at least 88 different genera. A natural products library (NPL) has also been constructed, consisting of 46,031 crude extracts, 28,739 partially purified fractions, and 650 pure NPs, which were made from 14,635 actinobacterial strains.

Current effort has been focused on sequencing the strain collection to establish the Natural Products Genomics Resource Center (NPGRC) for the broad scientific community.

Selected studies will be presented to highlight how to leverage the strain collection, the NPL, the NPGRC database, and the associated enabling technologies to transform the current paradigms of microbial natural product discovery and how to exploit this unique natural products resource to target emerging biology and accelerate drug discovery.

THURSDAY  I  APR. 28  I  3:30-4:30 PM CST  I  HYBRID SEMINAR
TO JOIN REMOTELY, GO TO: Z.UMN.EDU/BTI-2022-SPRING-SEMINARS

Michi Taga

Michi Taga

Michi Taga

University of California, Berkeley

Website
Corrinoids in Communities: Nutrient sharing in the microbial world

Microbial communities inhabit nearly all environments on earth. These communities are often composed of hundreds or more species that form networks of metabolic interactions.

Because metabolic interactions are complex and difficult to study at a molecular level, my research focuses on interactions involving one family of metabolites — corrinoid cofactors — as a model to understand metabolic interactions among bacteria. Corrinoids are the vitamin B12 family of cobalt-containing metabolites that function as enzyme cofactors in the majority of organisms. Corrinoids, like many other metabolites, are synthesized by only a fraction of bacteria that use them, but unlike other metabolites are a structurally diverse group of cofactors.

We have found that addition of particular corrinoids to communities derived from soil and from the human gut can alter the bacterial composition, leading to the exciting possibility that corrinoids may be used to manipulate microbiomes.

THURSDAY  I  APR. 14  I  3:30-4:30 PM CST  I  HYBRID SEMINAR
TO JOIN REMOTELY, GO TO: Z.UMN.EDU/BTI-2022-SPRING-SEMINARS

Ariel Furst

Ariel Furst

Ariel Furst BTI

Ariel Furst

Massachusetts Institute of Technology

Website
Bio-derived materials for sustainability & environmental remediation

Significant effort has been devoted to developing chemistries to effectively mimic biological processes. Despite decades of effort, these methods often fail to replicate the efficiency and selectivity of native systems.

We have found that by combining chemistry with the inherent activity of biomolecules and microbes, we can improve upon conventional technologies for clean energy and sustainability. Specifically, by combining biomolecular assembly with conventional electrocatalysis, we have improved the specificity and efficiency of electrocatalytic CO2 reduction.

Additionally, we have engineered bio-derived microbial coatings to enable their delivery to depleted soil. Finally, by combining electroactive microbes with engineered enzymes, we have developed a platform to degrade and electrochemically detect harmful pesticides.

Through these technologies, we have consistently found that the combination of chemistry and biomolecular engineering affords advantages beyond the capabilities of either technology alone.

THURSDAY  I  MAR. 31  I  3:30-4:30 PM CST  I  HYBRID SEMINAR

Randy Stockbridge

Randy Stockbridge

Randy Stockbridge BTI

Randy Stockbridge

University of Michigan

Website
The molecular basis for antiseptic resistance in bacteria

By providing broad resistance to ubiquitous disinfectants and antiseptics and other environmental biocides, transporters from the small multidrug resistance (SMR) family drive the spread of multidrug resistance cassettes among bacterial populations.

A fundamental understanding of substrate selectivity by SMR transporters is needed to identify the types of selective pressures that contribute to this process. In this talk, I will describe the molecular basis for the recognition of diverse substrates by SMR proteins, revealed through a combination of X-ray crystallography and electrophysiological approaches.

THURSDAY  I  MAR. 17  I  3:30-4:30 PM CST  I  REMOTE SEMINAR

Eric Helfrich

Eric Helfrich

BTI Eric Helfrich

Eric Helfrich

Goethe University Frankfurt

Website
Ecology-inspired & genomics-assisted discovery of bioactive natural products

Bacteria biosynthesize structurally diverse small molecules to interact with their environment. Many of the complex natural products involved in this “metabolic small talk” have been exploited as drugs in human and veterinary medicine.
Genome mining, i.e., the screening of genome sequences for their natural product biosynthetic potential, has revolutionized natural product discovery. Several generations of highly so-phisticated genome mining pipelines have been developed for the identification and annotation of natural product biosynthetic blueprints in genome sequences and to predict the structures of the associated metabolites.

Most genome mining pipelines are based on the seemingly universal biosynthetic principles deciphered for each natural product class. Natural products whose biosynthesis deviates from these seemingly universal rules, however, are in many cases overlooked by state-of-the-art genome mining algorithms. The corresponding non-canonical biosynthetic blueprints display an almost untapped treasure map for the identification of novel bioactive metabolites.
We develop artificial intelligence-based genome mining algorithms to chart this biosynthetic dark matter and to identify putative non-canonical biosynthetic transformations with the goal to expand natural product chemical space.

THURSDAY  I  FEB. 24  I  3:30-4:30 PM CST  I  REMOTE SEMINAR

Brandon Morinaka

Brandon Morinaka

BTI Brandon Morinaka

Brandon Morinaka

National University of Singapore

Website
Posttranslational formation of cyclophanes in bacteria

Cyclic peptide natural products are important chemical entities for human health and treating
diseases. The identification and application of methods that can robustly cyclize peptides has broad applications in research and industry.

Of particular interest are transformations that can create novel scaffolds for unique binding to biological targets and that protect the peptide from proteolytic degradation. The use of genome mining and synthetic biology expedites the discovery, design, production, and application processes to discover these biocatalysts.

I will share how our group used the radical SAM superfamily of enzymes as a starting point to identify a broadly distributed and novel subfamily that creates unique peptide-derived cyclophanes.

The cyclophane forming reaction is characterized by C(sp2)-Cb(sp3) bond formation on 3-residue motifs. Our objectives are to understand the chemical diversity that can be achieved using posttranslational cyclophane forming enzymes and then move to targeted applications relevant to infectious diseases.

Our results to date will demonstrate the range of peptide scaffolds that can be created, their potential uses, and direction of our research group.

THURSDAY  I  FEB. 10  I  3:30-4:30 PM CST  I  REMOTE SEMINAR