CC Hydrolases for Biocatalysis

Abstract

Although CC bond hydrolases are distributed widely in Nature, they has as yet have received only limited attention in the area of biocatalysis compared to their counterpart the C‐heteroatom hydrolases, such as lipases and proteases. However, the substrate range of CC hydrolases, and their non‐dependence on cofactors, suggest that these enzymes may have considerable potential for applications in synthesis. In addition, hydrolases such as the β‐diketone hydrolase from Rhodococcus (OCH) are known, that catalyse the formation of interesting chiral intermediates. Further enzymes, such as kynureninase and a meta‐cleavage product hydrolase (MhpC), are able to catalyse carbon‐carbon bond formation, suggesting wider applications in biocatalysis than previously envisaged. In this review, the distribution, catalytic characteristics and applications of CC hydrolases are described, with a view to assessing their potentialfor use in biocatalytic processes in the future.

Nucleophile Promiscuity of Natural and Engineered Aldolases

“…The term carboligase encompasses aldolases; thiamine diphosphate (ThDP)‐dependent enzymes; and proteins with promiscuous catalytic activity, such as lipases, proteases, 4‐oxalocrotonate tautomerase, C−C bond hydrolases, cyclases, and artificial aldolases produced by computational algorithms…”

Discovery and structural analysis of a phloretin hydrolase from the opportunistic human pathogen Mycobacterium abscessus

“…Designated as http://www.chem.qmul.ac.uk/iubmb/enzyme/EC3.7.1.1-EC3.7.1.23.html in the KEGG ENZYME database, C–C bond hydrolases are generally involved in the degradation pathways of various hydroxylated aromatic compounds, showing surprising structural and mechanistic diversity . Until now, four subclasses of C–C bond hydrolases have been well‐characterized, including α‐ and β‐diketone hydrolase, meta‐cleavage product hydrolase, Friedel–Crafts hydrolase and kynureninase . These enzymes typically employ a general base‐activated water or a residue such as serine as a nucleophile to attack at one of the carbonyl groups, leading to a tetrahedral alkoxide stabilized by an oxyanion hole formed at the active site.…”

“…Though sharing no obvious sequence similarity, most of the C-C bond hydrolases identified so far adopt the classical a/b hydrolase fold, a structural prototype commonly found in varieties of hydrolytic enzymes including proteases, lipases, and esterases [3]. One interesting exception is the 2,4-diacetylphloroglucinol (2, hydrolase PhlG from Pseudomonas fluorescens (PfPhlG), which shows the Bet v1like fold featuring an incomplete b-barrel sealed by a long a helix, quite distinct from a/b hydrolase fold [4].…”

Crystallization and preliminary X-ray diffraction analysis of a putative carbon–carbon bond hydrolase fromMycobacterium abscessus103

“…Enzymes that cleave carbon-carbon bonds have great potential as industrial biocatalysts for the production of high-value chemical building blocks owing to their diverse range of substrates and their catalytic independence of cofactors (Siirola et al, 2013). To date, 22 carbon-carbon bond hydrolases (EC 3.7.1.1-3.7.1.22) have been described in the KEGG enzyme database (Kanehisa & Goto, 2000).…”