White biotechnology for green chemistry: fermentative 2-oxocarboxylic acids as novel building blocks for subsequent chemical syntheses

Abstract

Functionalized compounds, which are difficult to produce by classical chemical synthesis, are of special interest as biotechnologically available targets. They represent useful building blocks for subsequent organic syntheses, wherein they can undergo stereoselective or regioselective reactions. "White Biotechnology" (as defined by the European Chemical Industry [ http://www.europabio.org/white_biotech.htm ], as part of a sustainable "Green Chemistry,") supports new applications of chemicals produced via biotechnology. Environmental aspects of this interdisciplinary combination include: Use of renewable feedstock Optimization of biotechnological processes by means of: New "high performance" microorganisms On-line measurement of substrates and products in bioreactors Alternative product isolation, resulting in higher yields, and lower energy demand In this overview we describe biotechnologically produced pyruvic, 2-oxopentaric and 2-oxohexaric acids as promising new building blocks for synthetic chemistry. In the first part, the microbial formation of 2-oxocarboxylic acids (2-OCAs) in general, and optimization of the fermentation steps required to form pyruvic acid, 2-oxoglutaric acid, and 2-oxo-D-gluconic acid are described, highlighting the fundamental advantages in comparison to chemical syntheses. In the second part, a set of chemical formula schemes demonstrate that 2-OCAs are applicable as building blocks in the chemical synthesis of, e.g., hydrophilic triazines, spiro-connected heterocycles, benzotriazines, and pyranoic amino acids. Finally, some perspectives are discussed.

Membrane-Bound, 2-Keto- d -Gluconate-Yielding d -Gluconate Dehydrogenase from “ Gluconobacter dioxyacetonicus ” IFO 3271: Molecular Properties and Gene Disruption

“…5KGA is a useful compound as a precursor of tartaric acid, xylaric acid, or a number of flavor compounds (18); thus, several attempts to produce 5KGA have been made with Glu-conobacter strains, and recently, exclusive production of 5KGA was accomplished with an FAD-GADH-defective mutant of Gluconobacter oxydans 621H (5). On the other hand, 2KGA itself is also a useful chemical and is applicable as a building block in the chemical synthesis of heterocyclic compounds and for regioselective and stereoselective chemical reactions (23).…”

Generation of the Human Metabolite Piceatannol from the Anticancer-Preventive Agent Resveratrol by Bacterial Cytochrome P450 BM3

“…However, an alternative to chemical synthesis of piceatannol is to use CYP102A1 enzymes to generate the metabolites of resveratrol. From the viewpoint of "White Biotechnology" as part of a sustainable "Green Biotechnology" (Stottmeister et al, 2005), the production of piceatannol via an enzyme reaction should be more effective and cleaner.…”

Simultaneous saccharification and fermentation of cellulose in ionic liquid for efficient production of α-ketoglutaric acid by Yarrowia lipolytica

“…1). KGA is a high-value organic that can extend the organismal lifespan (Chin et al 2014) and has a broad application such as a building block for synthesis of dietary supplements, pharmaceuticals, cosmetics, and heterocycles (Aurich et al 2012;Otto et al 2011;Stottmeister et al 2005;Zhou et al 2010). …”