Positioning Bacillus subtilis as terpenoid cell factory.

H Pramastya,E.Y Elfahmi,W.J Quax,S Sukrasno,Y Song

doi:10.1111/jam.14904

Abstract

SummaryIncreasing demands for bioactive compounds have motivated researchers to employ micro‐organisms to produce complex natural products. Currently, Bacillus subtilis has been attracting lots of attention to be developed into terpenoids cell factories due to its generally recognized safe status and high isoprene precursor biosynthesis capacity by endogenous methylerythritol phosphate (MEP) pathway. In this review, we describe the up‐to‐date knowledge of each enzyme in MEP pathway and the subsequent steps of isomerization and condensation of C5 isoprene precursors. In addition, several representative terpene synthases expressed in B. subtilis and the engineering steps to improve corresponding terpenoids production are systematically discussed. Furthermore, the current available genetic tools are mentioned as along with promising strategies to improve terpenoids in B. subtilis, hoping to inspire future directions in metabolic engineering of B. subtilis for further terpenoid cell factory development.

Highlights

The nature of Bacillus subtilisBacillus subtilis, a well-known Gram-positive bacterium, was one of the first organisms to have its genome successfully annotated
Residing as a special niche of the soil microbial ecosystem, B. subtilis has its strength in metabolite production required for survival (Yang et al.2016)
It is known that the bacterium has its capability to produce diverse secondary metabolites including polyketides and terpenoids acting as antimicrobial agents or being part of a defence mechanism against particular stresses (Calderone et al.2006; Butcher et al.2007; Bosak et al.2008; Kontnik et al.2008; Lee and Kim 2011; Barbosa et al.2015; Caulier et al.2019)

Summary

Introduction

A well-known Gram-positive bacterium, was one of the first organisms to have its genome successfully annotated. Residing as a special niche of the soil microbial ecosystem, B. subtilis has its strength in metabolite production required for survival (Yang et al.2016). It is known that the bacterium has its capability to produce diverse secondary metabolites including polyketides and terpenoids acting as antimicrobial agents or being part of a defence mechanism against particular stresses (Calderone et al.2006; Butcher et al.2007; Bosak et al.2008; Kontnik et al.2008; Lee and Kim 2011; Barbosa et al.2015; Caulier et al.2019). The reasons include the late development of diverse molecular tools and genome scale exploratory research that are required to facilitate precise engineering of the bacterium. This review deals with the progress on engineering of B. subtilis as the microbial cell factory.

Further strategies and conclusion

Conflict of Interest