RESUMO
Microbial enzymes from pristine niches can potentially deliver disruptive opportunities in synthetic routes to Active Pharmaceutical Ingredients and intermediates in the Pharmaceutical Industry. Advances in green chemistry technologies and the importance of stereochemical control, further underscores the application of enzyme-based solutions in chemical synthesis. The rich tapestry of microbial diversity in the oceanic ecosystem encodes a capacity for novel biotransformations arising from the chemical complexity of this largely unexplored bioactive reservoir. Here we report a novel ω-transaminase discovered in a marine sponge Pseudovibrio sp. isolate. Remote stereoselection using a transaminase has been demonstrated for the first time using this novel protein. Application to the resolution of an intermediate in the synthesis of sertraline highlights the synthetic potential of this novel biocatalyst discovered through genomic mining. Integrated chemico-genomics revealed a unique substrate profile, while molecular modelling provided structural insights into this 'first in class' selectivity at a remote chiral centre.
Assuntos
Biologia Computacional , Mineração de Dados , Genoma , Genômica , Transaminases/química , Transaminases/genética , Sequência de Aminoácidos , Biologia Computacional/métodos , Ativação Enzimática , Genômica/métodos , Modelos Moleculares , Estrutura Molecular , Filogenia , Estereoisomerismo , Relação Estrutura-Atividade , Transaminases/metabolismoRESUMO
Thyroglossal duct cysts develop from a persistent portion of the thyroglossal tract and have been described as occurring anywhere from the base of the tongue to the manubrium. We present two patients who presented with a cystic thyroid nodule due to an intrathyroid thyroglossal duct cyst. A fine-needle aspiration biopsy was performed, which revealed benign squamous cells. Upon exploration, the first patient was found to have a 2-cm cyst within the thyroid isthmus, and in the second patient, a 1-cm cyst was found in the right thyroid lobe. Pathologic analysis revealed the cyst to be lined by a squamous epithelium consistent with a thyroglossal duct cyst. The lesions were completely surrounded by normal thyroid tissue. There was no evidence of a remnant of the thyroglossal duct extending from the thyroid in the region of the cyst. Both patients were treated by thyroid lobectomy and isthmusectomy and have remained without evidence of recurrence. Intrathyroid thyroglossal duct cysts should be included in the differential of patients with cystic thyroid lesions. Fine-needle aspiration revealing benign squamous cells is usually diagnostic and may detect an occult carcinoma arising within the cyst. Surgical resection is curative and should include a Sistrunk procedure if a thyroglossal duct tract is present.
