Kevin Speina
Princeton University, USA
Title: Towards commodity scale production of ketones using a resilient fungal heme protein
Biography
Biography: Kevin Speina
Abstract
The non-reactive nature of aliphatic C-H bonds makes catalytic oxyfunctionalization, under ambient conditions profoundly difficult. Overcoming this challenge has the potential of transforming low cost, abundant hydrocarbons (i.e. methane, cyclooctane) into low cost precursor molecules capable of derivatization; an industrially advantageous enterprise. Fortunately, nature evolved enzymatic catalysts able to perform oxygenation onto relatively inert C-H bonds. Cytochrome P450s (P450) are a class of monooxygenases that incorporate molecular oxygen onto aliphatic C-H bonds with remarkable regio- and stereoselectivity. Unfortunately, P450 enzymes require a prohibitively expensive cofactor NAD(P)H and reductases to perform oxyfunctionalization reactions. A class of enzymes known as fungal aromatic peroxygenases (APOs) circumvents this limitation by using H2O2 as a co-substrate to generate the iron (IV) oxo porphyrin cation radical intermediate for C-H functionalization. APO enzymes are stable, extracellular, glycosylated proteins that have no sequence homology to P450 analogs yet have enhanced reactivity to P450 enzymes. Herein, a recently identified APO from Marasmius rotula [MroAPO] was found to be stable in the presence of organic solvents such as acetonitrile and acetone (up to 50v%). Even more remarkable is its propensity to form ketones from alkanes in high yields. Simply by adding 0.05% mol of MroAPO in acetone with excess oxidant, alkane substrates such as cyclooctane and decane are transformed to the corresponding ketone products with 90+% yield. A total turnover number (TTN) of 50000 was calculated for cyclooctane oxidation. This is the second highest TTN reported for cyclooctane. Astonishingly, enzymatic reactions with C10-C6 linear alkanes results in the 2-ketone product, with minute amounts of side products. The 2-ketone products are desirable for the fragrance and food industries. Thus, the reactions catalyzed by MroAPO enzymes have promising biotechnical potential insofar their versatility is unmatched to any known catalyst.