Fusarium sp. HKF15 is an isolate from effluent treatment plant which produces bikaverin. Bikaverin is a polyketide having antitumor and antibiotic potential. Acetyl coenzyme A is a common precursor for bikaverin as well as carotenoids and gibberellins. A polyketide synthase gene bik1 is responsible for bikaverin production whereas, hydroxymethyl glutaryl coenzyme A reductase (hmgR) and farnesyl pyrophosphate synthase (fpps) are carotenoid and gibberellin pathway genes. Aim of this study was assessing siRNA mediated gene silencing for bikaverin overproduction with down-regulation of carotenoid and gibberellin pathway. HKF15 protoplasts derived from glucose grown culture were treated with 200 pmol ml(-1) hmgR and fpps siRNAs separately. Along with down-regulation of target genes, there was 2.4-fold increase in bik1 gene expression. The silencing was effective till 48 h with a 41% increase in bikaverin production. The study proposes a strategy for manipulation of physiology towards desired secondary metabolite overproduction. (C) 2014 Elsevier Ltd. All rights reserved.