Economical production of androstenedione and 9α-hydroxyandrostenedione using untreated cane molasses by recombinant mycobacteria.

ABSTRACT

Production of androstenedione (AD) and 9α-hydroxyandrostenedione (9α-OH-AD) by recombinant mycobacteria using untreated cane molasses and hydrolysate of mycobacterial cells (HMC) was investigated for the first time. B-vitamins feeding experiment and reverse transcription-PCR analysis showed that propionyl-CoA carboxylase (PCC) plays an important role in the phytosterol biotransformation of mycobacteria. The respective AD and 9α-OH-AD conversion ratios were increased by 2.91 and 1.48 times through coexpression of PCC and NADH dehydrogenase. The highest conversion ratios of AD and 9α-OH-AD obtained by using a co-feeding strategy of cane molasses and HMC reached 96.38% and 95.04%, respectively, and the total costs of carbon and nitrogen sources for the culture medium were reduced by 29.89% and 49.49%, respectively. Taking the results together, untreated cane molasses and HMC can be used for the economical production of steroidal pharmaceutical precursors by mycobacteria. This study offers an economical and green strategy for steroidal pharmaceutical precursor production.