The process of subduction has significant influence on the geochemical evolution of the crust and mantle, and subduction-related magmatism may have been an important mechanism for the growth of continental crust over time. Extensive exposure of the mid-crustal levels of an ancient, exhumed continental arc in the Transantarctic Mountains provides an exceptional opportunity to study the metamorphic and magmatic processes associated with an archetypal subduction zone. The belt of multiply deformed metamorphic rocks and granitoid batholiths records convergence and subduction of paleo-Pacific oceanic lithosphere beneath East Antarctica during the Neoproterozoic–Paleozoic Ross orogeny. These rocks are especially well exposed in the southern Victoria Land (sVL) segment of the Transantarctic Mountains––the largest ice-free area of Antarctica. The metamorphic and igneous rocks in sVL provide insights into the early stages of convergent-margin tectonism, the compositional diversity of subduction-related magmatism, and the relative roles of crustal growth and recycling in continental arcs.

In Chapter 1 of this dissertation, garnet Lu-Hf and monazite U-Pb geochronology—combined with petrography, mineral chemistry, and thermobarometry—reveal a Barrovian-style metamorphic history that predated the dominant phase of magmatism in sVL. The geochronology data from this study provide one of the oldest records of tectonism along the Ross orogen. The results are consistent with a tectonic model that involves shortening across the margin of East Antarctica prior to the major phase of subduction-related magmatism.

Chapter 2 explores the age and magma sources of a large subduction-related igneous complex in the Dry Valleys area. Zircon U-Pb geochronology demonstrates that the period of magmatism in the Dry Valleys was relatively short-lived compared to other segments of the Ross orogen. Whole-rock geochemistry and Hf isotopes in zircon reveal the assimilation of ancient crust during the differentiation of juvenile magmas that were likely derived from an enriched sub-continental lithospheric mantle source. A compilation of Nd and Sr isotope data from granitoids from along the Ross orogen suggest that enriched lithospheric mantle may have been a common juvenile magma source along the arc.

In Chapter 3, a comprehensive geochemical, geochronologic, and isotopic investigation of the magmatism in sVL explores the conspicuous occurrence of alkaline silicate rocks and carbonatites—most commonly associated with intraplate and continental-rift magmatism—within the continental arc. The alkaline magmatism was partially contemporaneous with the emplacement of large sub-alkaline igneous complexes in adjacent segments of the arc. The isotopic and trace element composition of the alkaline and subalkaline rocks suggests derivation from geochemically enriched sources—potentially metasomatized sub-continental lithospheric mantle. Despite enriched isotopic and trace element compositions that broadly resemble recycled continental crust, binary mixing and assimilation-fractional crystallization models indicate that crustal growth may have been dominant over crustal reworking in the sVL magmatism.

Polyketide synthases (PKSs) are remarkable enzymes. The diverse products from naturally ocurring PKSs have saved lives due to their useful medicinal qualities and inspired chemists to push the envelope on size and complexity in their synthetic pursuits. More recently, these enzymes have been modified to produce "unnatural" natural products--including close analogs of naturally occurring products as well as molecules wholly unknown to nature. These engineering pursuits have been enabled by an increasingly sophisticated understanding of PKS mechanics as well as technologies of the genomics era like inexpensive DNA sequencing and synthesis. In the doctoral work presented in this thesis, I will describe studies that have expanded our understanding of PKS biochemistry and demonstrated the production of an extremely economic and environmentally important small molecule from an engineered polyketide synthase.

Chapter 1 will begin with a discussion of the current state of the art and challenges associated with engineering these enzymes as well as offering opinions about routes forward to narrow the considerable gap between the promise and reality of engineered PKSs. This will be followed by a brief review of the PKS system responsible for borrelidin biosynthesis with a focus on features that make it unusual and attractive for engineering purposes.

In Chapter 2, I will present a study describing the first in vitro characterization of the unusual carboxyacyl-processing borrelidin polyketide synthase. It was found that the loading module has a specific requirement for carboxylated substrates of a specific stereochemistry, whereas the first extension module is comparatively promiscuous in its ability to extend carboxy- and descarboxy substrates with no apparent stereoselectivity.

The following chapter describes engineering efforts which exploit borrelidin PKS' diacid processing abilities towards the production of the commodity chemical, adipic acid. Extensive intermediate analysis using mass spectrometry revealed an unexpected difficulty in dehydrating the 3-hydroxyadipic-ACP intermediate, which was overcome in part by judicious chimeric junction selection and utilization of a dehydratase domain that may better tolerate carboxylated substrates. Provision of a thioesterase led to the first demonstration of adipic acid production from an engineered polyketide synthase.

In the final data chapter, I describe a preliminary characterization of a module in the borrelidin cluster which performs three iterative condensations rather than the single extension performed in canonical type I modular PKS systems. It was proven in vitro for the first time that the isolated module is necessary and sufficient for iteration to occur and that the identity of the starter substrate has a profound effect on the distribution of extension products. Based on observations from time course experiments and co-incubation with the downstream extension module, a model for chain-length control in this unusual module is proposed.

The last chapter provides a brief summary of the principal findings described in this work and suggests experiments that will form the foundation of future efforts to improve our understanding of and ability to engineer these fascinating molecular assembly lines.