Emerging developments and innovations in the construction of microbial cell factories for the improved production of S-adenosylmethionine

Abstract

S-adenosylmethionine (SAM) is a metabolite of great biological and pharmacological significance. Its biochemical roles can only be described as central for life. It is produced in almost every organism, and its chemical structure enables it to participate in at least three classes of group transfer reactions as the group donor. It has been employed in treatment of osteoarthritis, depression, Alzheimer’s disease, liver disease and fibromyalgia. Its enzymatic synthesis requires the participation of L-methionine and ATP as substrates and methionine adenosyltransferase the enzyme. Meeting the ever-increasing demand for the compound requires increasing production. A number of strategies have been employed to achieve sustainable SAM production. Principal focus has been on improving its production by microbial fermentation. Enzyme engineering, metabolic engineering, conditions optimisation are some of the biotechnological approaches the have been explored to achieve improved microbial SAM production. The successes achieved by the methods have mostly been mixed. Presently industrial SAM production is by yeast fermentation, applying high density cultures of Pichia pastoris or Saccharomyces cerevisiae. This review provides a concise report of the present achievements of methods that have been applied in Escherichia coli, P. pastoris and S. cerevisiae to achieve sustainable improvement in industrial SAM production, highlights contemporary strategies and also suggests potential methods that could be channelled to the same goal.