A screening of 416 strains (71 bacterial strains, 45 actinomycetes, 59 yeast, 60 basidiomycetes, 33 marine fungi and 148 filamentous fungi) has been performed to look for microorganisms that display reductase activity in the absence of oxidase activity. A new microorganism, Diplogelasinospora grovesii IMI 171018 (a nonpathogen strain), was isolated and showed very high activity and stereoselectivity in the reduction of cyclic ketones. The fungus was selected due to its selectivity towards monocyclic and bicyclic ketones and its easy culture conditions, which allow an easy scale-up. D. grovesii is more active in the reduction of conventional ketones than S. cerevisiae type II (from Sigma) and can work in the presence of high ketone concentrations (<60 mM). Comparative molecular fields analysis (CoMFA) has been applied in order to explain the steric and electronic properties of the carbonylic compound to be substrate for the microbial alcohol reductase. The CoMFA model is highly predictive (q2 = 0.549) and can be used to explain and to predict the structure of ketones that can or cannot be reduced by this microorganism. © 2004 Elsevier Ltd. All rights reserved.