Systems biology and metabolic engineering of Rhodococcus for bioconversion and biosynthesis processes

Abstract

Rhodococcus spp. strains are widespread in diverse natural and anthropized environments thanks to their high metabolic versatility, biodegradation activities, and unique adaptation capacities to several stress conditions such as the presence of toxic compounds and environmental fluctuations. Additionally, the capability of Rhodococcus spp. strains to produce high value-added products has received considerable attention, mostly in relation to lipid accumulation. In relation with this, several works carried out omic studies and genome comparative analyses to investigate the genetic and genomic basis of these anabolic capacities, frequently in association with the bioconversion of renewable resources and low-cost substrates into triacylglycerols. This review is focused on these omic analyses and the genetic and metabolic approaches used to improve the biosynthetic and bioconversion performance of Rhodococcus. In particular, this review summarizes the works that applied heterologous expression of specific genes and adaptive laboratory evolution approaches to manipulate anabolic performance. Furthermore, recent molecular toolkits for targeted genome editing as well as genome-based metabolic models are described here as novel and promising strategies for genome-scaled rational design of Rhodococcus cells for efficient biosynthetic processes application.

The Complete Genome Sequence and Structure of the Oleaginous Rhodococcus opacus Strain PD630 Through Nanopore Technology

“…However, pRoPD630_1 included a significantly higher number of genes associated to all of these metabolisms as compared to pRoPD630_2 and pRoPD630_3. In particular, pRoPD630_1 showed a high number of genes associated with xenobiotics degradation and fatty acid catabolism/anabolism that are the metabolic capacities mostly studied for this strain and in general for R. opacus species ( Anthony et al, 2019 ; Donini et al, 2021 ). Conversely, in the PD630 genome version of ( Chen et al, 2013 ), these genes were distributed over the seven scaffolds that were erroneously identified as separate plasmids.…”

“…The high versatility and adaptability of Rhodococcus strains is partly related with large and complex genomes (up to 10.1 Mbp) including high genetic redundancy and the presence of several circular and linear (mega)plasmids, which harbour peculiar catabolic and biosynthetic genes ( Cappelletti et al, 2019 ). Within Rhodococcus genus, R. opacus strain PD630 is considered a model oleaginous strain for its ability to produce and accumulate lipids (mostly triacyglycerols, TAGs) using different carbon sources, including low-cost and renewable resources such as lignocellulose ( Alvarez et al, 1996 ; Anthony et al, 2019 ; Cappelletti et al, 2020 ; Alvarez et al, 2021 ; Donini et al, 2021 ). Notably, under specific growth conditions, this strain is capable of accumulating up to 80% of its cellular dry weight in TAGs ( Alvarez and Steinbüchel, 2002 ); that is a rare feature in the prokaryotic and eukaryotic kingdoms.…”

“…Multi-omic approaches have been applied to obtain system-level information about metabolic and regulatory pathways involved in these biosynthetic processes. Novel molecular tools for genome editing (CRISPR/Cas9 and recombineering) have been recently developed highlighting the possible utilization of R. opacus PD630 as synthetic biology platform for lipids production ( Donini et al, 2021 ; Liang and Yu, 2021 ).…”

Rhodococcus strains as a good biotool for neutralizing pharmaceutical pollutants and obtaining therapeutically valuable products: Through the past into the future

“…The UN General Assembly proclaimed 2022 the International Year of Basic Sciences for Sustainable Development (IYBSSD 2022). The fundamental tasks touched upon in this review will be solved through active implementation of advanced approaches, such as genomics, metagenomics, proteomics, transcriptomics, and metabolomics ( Chen et al, 2014 ; Henson et al, 2018 ; Sengupta et al, 2019 ; Pacwa-Płociniczak et al, 2020 ; Donini et al, 2021 ; Mishra et al, 2021 ; Táncsics et al, 2021 ; Firrincieli et al, 2022 ). The use of such “omics technologies” allows us to obtain a comprehensive view of rhodococcal populations, their mechanisms of interaction with pharmaceuticals, their metabolic machinery, evolution and adaptation, genetic regulation and molecular biological aspects ( Chevrette et al, 2020 ; González-Benítez et al, 2021 ; Mishra et al, 2021 ; Undabarrena et al, 2021 ).…”

Prospect of metabolic engineering in enhanced microbial lipid production: review

“…There have been four putative genes identified in R. opacus PD630. Overexpression of TE2 and TE4 increased the lipid content and cell biomass by 46% and 44%, respectively, in comparison to the parent strain [132]. In another study, R. opacus strains were engineered in multiple ways to increase the production of FFAs, FAEE, and long-chain fatty acids (LCFAs).…”