General Description

Dodecanedioic acid serves multiple significant roles across various fields, from enhancing metabolic flexibility beneficial for individuals with type 2 diabetes by improving skeletal muscle glycogen stores and fatty acid utilization, to sustainable production via biotransformation using Candida tropicalis, optimizing yields for industrial applications such as polyamide nylon-6,12 synthesis. Furthermore, Dodecanedioic acid is instrumental in the synthesis of plate-like hydroxyapatite, crucial for head and neck reconstruction scaffolds, by regulating HA morphology to support cartilage regeneration effectively. This multifaceted utility demonstrates Dodecanedioic acid's importance in medical, industrial, and tissue engineering applications, highlighting its potential in improving metabolic health and advancing sustainable production and regenerative medicine.

Figure 1. Dodecanedioic acid

Physiological role

Dodecanedioic acid plays a significant role in enhancing metabolic flexibility, particularly beneficial for individuals with type 2 diabetes mellitus. Metabolic flexibility is the capacity of skeletal muscle to efficiently switch between glucose and fat oxidation in response to various signals. In conditions like type 2 diabetes and obesity, this flexibility is notably compromised. Dodecanedioic acid has been identified as a substrate that can improve skeletal muscle glycogen stores through succinyl-CoA formation, which not only helps in delaying fatigue but also enhances fatty acid utilization without impacting insulin secretion. Research involving both healthy volunteers and type 2 diabetic subjects demonstrated that oral administration of Dodecanedioic acid, compared to glucose or water, significantly aids in sustaining prolonged moderate-intensity exercise. The metabolism of Dodecanedioic acid, as analyzed through mathematical modeling, indicates its rapid oxidation and contribution to energy expenditure without inhibiting lipolysis, unlike glucose ingestion. This suggests that Dodecanedioic acid could be an effective energy substrate during physical activity, reducing muscle fatigue and promoting better utilization of fats, thereby offering a potential dietary intervention for improving metabolic health in diabetic patients. ¹

Production by biotransformation

Dodecanedioic acid is a crucial compound for the chemical industry, primarily serving as a precursor for manufacturing polyamide nylon-6,12, which is notable for its use in heat and chemical-resistant applications. Traditional methods of synthesizing Dodecanedioic acid face challenges such as high energy requirements and the costly removal of by-products, prompting the need for more sustainable, bio-based production methods. A promising approach involves the biotransformation of low-cost plant-oil derivatives using the yeast Candida tropicalis. This process capitalizes on the ability of C. tropicalis to convert petrochemical-based n-dodecanes into dicarboxylic acids through targeted functionalization. Specifically, the production process has been enhanced by utilizing dodecanoic acid methyl ester, derived from coconut oil transesterification, as a substrate in whole-cell biotransformation. By optimizing various process parameters, including a gradual pH adjustment, an effective substrate feeding strategy, and monitoring transcriptional profiles, a significant yield of 66 g/L Dodecanedioic acid was achieved in a small-scale, highly reliable bioreactor system, marking a substantial advancement in sustainable Dodecanedioic acid production. ²

Applications in the synthesis of plate-like hydroxyapatite

Dodecanedioic acid plays a pivotal role in the synthesis of plate-like hydroxyapatite (HA), which is specifically designed to enhance chondrogenic cell proliferation. In the context of head and neck reconstruction, there is a critical need for scaffolds that not only possess mechanical strength to maintain specific forms but also support cartilage regeneration. Traditional HA enhances the mechanical strength of hydrogels used in such regenerative processes; however, the innovation here lies in the ability to control chondrogenic cell behavior through the morphology of HA. By employing a hydrothermal process that utilizes Dodecanedioic acid, researchers have successfully regulated HA morphology, resulting in a novel form of HA (DD:HA) that significantly promotes the proliferation and differentiation of chondrocytes compared to its counterparts synthesized with other organic acids like oleic acid (OA:HA). The study reveals that DD:HA exhibits superior surface properties, including increased roughness and hydrophilicity, which are conducive to better cell viability and differentiation. This highlights Dodecanedioic acid's crucial role in developing advanced materials for chondrocyte regeneration, showcasing its potential in enhancing tissue engineering applications. ³

Reference

1. Salinari S, Bertuzzi A, Gandolfi A, et al. Dodecanedioic acid overcomes metabolic inflexibility in type 2 diabetic subjects. Am J Physiol Endocrinol Metab. 2006;291(5):E1051-E1058.

2. Funk I, Rimmel N, Schorsch C, Sieber V, Schmid J. Production of dodecanedioic acid via biotransformation of low cost plant-oil derivatives using Candida tropicalis. J Ind Microbiol Biotechnol. 2017;44(10):1491-1502

3. Wint WY, Horiuchi N, Nozaki K, Nagai A, Yamashita K, Miyashin M. Plate-like hydroxyapatite synthesized from dodecanedioic acid enhances chondrogenic cell proliferation. Biomed Mater Eng. 2019;30(4):375-386.