Title: Biosynthetic Enzymes: Tools and Targets

Speaker: Prof. Emily J Parker

Abstract: Our work is focused on understanding the mechanisms of complex biosynthetic machinery and putting it to use.

Protein conformational changes and dynamics play critical roles in delivering complex enzyme function.  We have examined the roles of subtle communication networks and conformational adjustments in delivering both catalysis and allosteric functionality to enzymes that play key roles in aromatic amino acid biosynthesis, allowing us to engineer enzymes with new allosteric functionality.

Many organisms, including plants and microbes, utilise unique armouries of bioactive compounds provide protection against predators and enable establishment of new ecological niches.  Although bioactive compounds are used widely for industrial and pharmaceutical applications their diversity remains largely untapped as many compounds are produced in very low yields and the complexity of their biosynthesis is yet to be fully understood.  In our work we have identified the gene cluster responsible for biosynthesis for a specific indole diterpene. By using heterologous expression, employing our new molecular biology tools that enable combinatorial gene combinations, we have reconstructed the biosynthetic pathway in an alternative fungal host. Our work has uncovered a large natural product compound array, which allows access to many known and novel compounds.

1. Fan Y, Cross PJ, Jameson GB, Parker EJ. Exploring modular allostery via interchangeable regulatory domains. Proc. Natl. Acad. Sci. U. S. A. 2018, 115, 3006-3011.
2. van Dolleweerd CJ, Kessans SA, Van de Bittner KC, Bustamante LY, Bundela R, Scott B, Nicholson MJ & Parker EJ. 2018, MIDAS: A modular DNA assembly system for synthetic biology. ACS Synth Biol 7, 1018-29.
3. Van de Bittner KC, Nicholson MJ, Bustamante LY, Kessans SA, Ram A, van Dolleweerd CJ, Scott B & Parker EJ. 2018, Heterologous biosynthesis of nodulisporic acid F. J Am Chem Soc 140, 582-85.
4. Jiao, W., Lang, E. J., Bai, Y., Fan, Y., and Parker, E. J. 2020, Diverse allosteric componentry and mechanisms control entry into aromatic metabolite biosynthesis, Curr. Opin. Struct. Biol. 65, 159-167.