Industrial production of paenibacillin, and similar rare antimicrobial peptides, is hampered by low productivity of the producing microorganisms and lack of efficient methods to recover these peptides from bioreactor end products. Preliminary data showed that paenibacillin was preferentially partitioned in foam accumulated during growth of the producer, Paenibacillus polymyxa, in aerated liquid media. This research was initiated to improve the production and recovery of paenibacillin in bioreactors by maximizing partitioning of the antimicrobial in the collected foam. This was completed through harvesting foam continuously during antimicrobial production, using modified bioreactor, and optimizing bioreactor conditions through response surface methodology (RSM). Experiments proved that the significant parameters and their optimal conditions for antimicrobial concentration in the foam were: incubation at 30°C for 23h with airflow of 0.95 LPM, and agitation speed of 450 RPM. These conditions increased paenibacillin concentration, predicted by RSM, from 16 µg/ml in bioreaction without foam collection to 743 µg/ml collected in foamate. The optimized conditions also almost doubled the yield of paenibacillin collected in foam (12,674 µg) when compared to that obtained without foam collection (6,400 µg). Results of this study could improve the feasibility of commercial production and downstream processing of paenibacillin and similar novel antimicrobial peptides.