The invention provides methods of producing secondary metabolites and under recombinant products oxygen-limited or anaerobic culture conditions. The methods include providing a porous substrate having a first side and a second side and which has a biofilm of microorganisms attached to the first side thereof, and causing a nutrient solution to flow through the biofilm and the substrate in a direction from the first side thereof to the second side thereof under oxygen-limited or anaerobic culture conditions. The microorganisms include Clostridium sp., Bacillus sp., Pseudomonas sp. Vibrio sp., Serratia sp., Rhodopseudomonas sp., Anaeromyxobacter sp., Desulphovibrio sp., and Candida sp., Lactococcus lactis, Escherichia coli, Bacillus subtillus, Pichia sp., Candida sp., Hansenula polymorpha and Saccharomyces cerevisiae.