Author Archives: Duncan Smith

Rebecca Goss

I am a bioorganic chemist/chemical biologist with research interests in the biosynthesis of natural products at the chemical and genetic level. Specifically, my research focuses on natural products with important medicinal properties and in understanding how biosynthetically intriguing motifs within these compounds are assembled. From this vantage point we harness individual enzymes as convenient tools for organic synthesis, and employ a combination of synthetic chemistry and synthetic biology to harness entire biosynthetic pathways in order to enable expeditious access to libraries of medicinally relevant compounds. These libraries may be used to gain a greater understanding as to how the drug acts at the molecular level within the cell. I am establishing a national and international reputation presenting numerous invited research seminars across the world including Brazil, Capetown, Delhi, Kyoto, Denver and, Boston, in addition to invited seminars at numerous European departments and companies.

Rebecca Goss’ CV

Antoine Abou Fayad

I am a highly motivated BioOrganic Medicinal Chemist with research interests in the synthesis,
biosynthesis and biosynthetic manipulation of natural products. Through my MSc I have developed skills in organic synthesis and I have extended these skills in biochemistry further through my PhD. I have a deep interest in the medical research field especially in the discovery and isolation of antibiotics. I am interested in how biosynthetic pathways may be harnessed in order to create natural products of my own design with improved biological. Combining synthetic chemistry and biosynthesis provides expeditious access to series of otherwise synthetically intractable natural product analogues. These libraries may be used to gain a greater understanding of the drug’s structure activity relationships.

Antoine Abou Fayad’s CV

Tania Triscari Barberi

I am a Molecular Microbiologist with research interests in the development of whole cell catalysts, with particular focus on engineering microbial biofilms as platform for biotransformations. Biofilms are known for their robustness and ability to withstand harsh environmental conditions, therefore I am working toward harnessing these features to develop a biocatalytic biofilm platform in which enzymes of choice are produced, enabling me to carry out biotransformations in continuous flow systems.

Tania Triscari Barberi’s CV

Michael Corr

I am an organic/bioorganic chemist with research interests in the synthesis and biosynthesis of natural products. My previous work has included the synthesis and isolation of highly reactive superelectrophile compounds and the synthesis of fluorinated derivatives of natural products. My current research focuses on marrying biosynthesis and synthetic chemistry to generate new natural product analogues.

Michael Corr’s CV

Maoluo Gan

My research work focused on the natural products chemistry, including the isolation and structure determination of new bioactive natural, genome mining, and genetic manipulation of bioactive natural product biosynthesis. I have developed skills in the isolation and purification, structure elucidation, organic synthesis of natural products through my MSc and PhD. After that, my research centres on the screening of new antibiotics with the activity against drug-resistant-pathogens, particularly against tuberculosis, discovering new antibiotics from marine derived microbes, especially water-soluble antibiotics. As the traditional process of discovering new bioactive natural products is generally long and laborious, I am interested in the methodology of dereplication of microbial natural products by combing chemical LC-UV-MS and bioinformatics methods. In addition, I have a deep interest in the genetics and genetic manipulation of bioactive natural product biosynthesis.

Maoluo Gan’s CV

Frida Michailidou

I am a synthetic chemist/ chemical biologist with a particular interest in the biosynthesis of natural products, and am especially fascinated by the enzymes involved in in sugar and nucleoside biosynthesis and modification. I am passionate about biocatalysis, considering it the most striking and environmentally-friendly approach to synthesis. I am currently working on a very interdisciplinary project, combining synthetic chemistry, molecular biology and enzymology. Specifically, I am investigating the biosynthesis of the nucleoside moiety of pacidamycins, by focusing on the enzymes involved. Combining synthetic chemistry and heterologous expression, kinetic and crystallisation studies I aim to obtain a better understanding of the function of these enzymes, that could be potentially used for the generation of nucleoside antiviral targets.

Frida Michailidou’s CV

Filipins: the first antifungal “weed killers” identified from bacteria isolated from the trap-ant

Allomerus ants ensure that they have sufficient nitrogen in their diet by trapping and consuming other insects. In order to construct their traps, like the more extensively studied leaf cutter ants, they employ fungal farming. Pest management within these fungal cultures has been speculated to be due to the ants’ usage of actinomycetes capable of producing antifungal compounds, analogous to the leafcutter ant mutualism. Here we report the first identification of a series of antifungal compounds, the filipins, and their associated biosynthetic genes isolated from a bacterium associated with this system.

Gao H, Grüschow S, Barke J, Seipke RF, Hill LM, Orivel K, Yu DW, Hutchings M, Goss RJM

RSC Adv. 2014, 4, 57267

Mechanism of action of the uridyl peptide antibiotics: an unexpected link to a protein–protein interaction site in translocase MraY

The pacidamycin and muraymycin uridyl peptide antibiotics show some structural resemblance to an Arg-Trp-x-x-Trp sequence motif for protein–protein interaction between bacteriophage [curly or open phi]X174 protein E and E. coli translocase MraY. Members of the UPA class, and a synthetic uridine–peptide analogue, were found to show reduced levels of inhibition to F288L or E287A mutant MraY enzymes, implying that the UPAs interact at this extracellular site as part of the enzyme inhibition mechanism.

Rodolis MT, Mihalyi A, Ducho C, Eitel K, Gust B, Goss RJM, Bugg TDH

Chem. Commun. 2014, 50, 13023

Access to High Value Natural and Unnatural Products through Hyphenating Chemical Synthesis and Biosynthesis

Access to natural products and their analogues is crucial. Such compounds have, for many years, played a central role in the area of drug discovery as well as in providing tools for chemical biology­. The ability to quickly and inexpensively acquire genome sequences has accelerated the field of natural product research. Access to genomic data coupled with new technologies for the engineering of organisms is resulting in the identification of large numbers of previously undiscovered natural products as well as an increased understanding of how the biosynthetic pathways responsible for the biogenesis of these compounds may be manipulated. This short review summarizes and reflects upon approaches to accessing natural products and has a particular focus on approaches combining molecular biology and synthetic chemistry.

Mahoney KPP, Smith DRM, Bogosyan EJA, Goss RJM

Synthesis 2014, 46 (16), 2122