Regulation on Pathway Metabolic Fluxes to Enhance Colanic Acid Production in Escherichia coli.

Colanic acid (CA) is a natural polysaccharide macromolecule with rich and unique biological properties and is a promising candidate for use in food and cosmetics. To date, the efficient biosynthesis of CA and the influence of product accumulation on the strains used have yet to be precisely investigated. Herein, bottlenecks in the CA metabolic pathway were untangled by finely regulating the expression of manA, cpsG, fcl, and rcsA. Engineered strains produced CA at >1 g/L in shake flasks without dependence on cold temperatures, and it was verified in a 1 L bioreactor with a titer up to 18.64 g/L within 24 h. The accumulation of CA caused a decrease in the saturated fatty acid content (represented by C16:0 and C18:0) in the cell membrane. This study demonstrated pathway engineering for efficient CA production in cell factories and provided insights into the barriers and solutions faced in the biosynthesis of natural products.

[Analysis of OCRL gene variant in a Chinese pedigree affected with Lowe syndrome].

OBJECTIVE: To explore the genotype-phenotype correlation of a Chinese pedigree affected with Lowe syndrome. METHODS: Whole exome sequencing (WES) and Sanger sequencing were carried out for the proband and members of his pedigree. RESULTS: The proband, a 3-year-and-5-month-old male, presented with multiple anomalies including congenital cataract, glaucoma, brain dysplasia, renal dysfunction and cognitive impairment. WES revealed that he has harbored a novel hemizygous missense variant of the OCRL gene, namely NM_000276.3: c.1255T>C (p.Trp419Arg) (GRCh37/hg19), which was derived from his unaffected mother. The same variant was not found in his elder brother who was healthy. The variant was predicted to be pathogenic according to ACMG/AMP guideline. Compared with previously reported cases of Lowe syndrome, our patient has displayed rare features including corpus callosum dysplasia, reduction of white matter, cerebral hypoplasia, laryngomalacia, sebaceous cyst, recurrent eczema, cryptorchidism, hypoglycemia and irritability. CONCLUSION: Above finding has expanded the mutational spectrum of the OCRL gene, enriched clinical features of Lowe syndrome, and enabled genetic counseling for this pedigree.