We recently reported on the capsular polysaccharide (CP) synthesis (cps) genes of the oral streptococci, Streptococcus anginosus. In this study, we investigate the effects of carbon dioxide (CO2), bicarbonate (HCO3) and unsaturated fatty acids (UFAs) on CP synthesis of S. anginosus. We found that CP production increased when bacteria were exposed to high concentrations of CO2. This increase was similarly observed in the presence of sodium bicarbonate (NaHCO3) under atmospheric condition. Since ectopic expression of carbonic anhydrase, which converts CO2 to HCO3, eliminated the requirement for CO2 in CP production and growth of S. anginosus lacking this enzyme, it seemed that HCO3 is an essential factor for CP production. Furthermore, UFAs also stimulated the CP production. Promoter-reporter assay and quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis confirmed that stimulation of CP production occurs at the transcription level. The results of the promoter assays suggest that the expression and stimulation of cps genes by HCO3 or UFAs require the cpsA gene, which is located in the first position of the cps operon. With respect to the relationship between HCO3 and UFAs, HCO3 may stimulate UFA synthesis pathway at transcription level. Therefore, it is possible that UFAs are definitive signals for the CP production in S. anginosus. (C) 2019, The Society for Biotechnology, Japan. All rights reserved.