Biological sciences pose a unique set of engineering challenges due to incomplete understanding of natural biological systems. Currently, sequencing of macromolecules i.e., DNA (deoxyribose nucleic acid) and proteins obtained from living cells has provided significant information, which is available in different database repositories. These databases comprising of genomic sequences and amino acid sequences (proteins) are utilized in genetic engineering of biological systems to increase the production of chemicals and pharmaceuticals for improving plant and animal health. Recently, synthetic biology approaches are being employed in rational and high-throughput biological engineering to enhance the production of beneficial chemicals. Recent molecular and bioinformatics tools have enabled to redesign the entire biological cycle, including construction of synthetic DNA inside the cell or replacement of entire genome to create synthetic organisms by utilizing gene libraries, computational tools and interfaces. This review describes the genomic, proteomic and phylogenetic databases, which may be utilized for designing and manipulation of synthetic gene circuits to perform novel functions and desired phenotypes in different ecosystems. In addition, synthetic biology approaches were discussed for designing biological systems for production and release of specific metabolic products. The progress and challenges faced in computational methodology and synthetic biology approaches are discussed for their potential applications in synthetic biology.