Pathway Design, Engineering, and Optimization

Abstract

The microbial metabolic versatility found in nature has inspired scientists to create microorganisms capable of producing value-added compounds. Many endeavors have been made to transfer and/or combine pathways, existing or even engineered enzymes with new function to tractable microorganisms to generate new metabolic routes for drug, biofuel, and specialty chemical production. However, the success of these pathways can be impeded by different complications from an inherent failure of the pathway to cell perturbations. Pursuing ways to overcome these shortcomings, a wide variety of strategies have been developed. This chapter will review the computational algorithms and experimental tools used to design efficient metabolic routes, and construct and optimize biochemical pathways to produce chemicals of high interest.

Precise Quantification of Translation Inhibition by mRNA Structures that Overlap with the Ribosomal Footprint in N-terminal Coding Sequences

“…A mRNA's translation rate is controlled by its sequence through the collective action of several ribosome-mRNA interactions (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11), creating a complicated sequence-function relationship. Developing a precise and predictive understanding of these interactions has become essential to controlling protein expression levels for a wide variety of biotechnological applications (12), including biosensor development (13)(14)(15), metabolic pathway engineering (16)(17)(18)(19)(20)(21)(22)(23)(24), and genetic circuit engineering (25)(26)(27). Within this sequencefunction relationship, different portions of the mRNA play distinct roles, though most studies have largely focused on how the bacterial ribosome binding site sequence affects the mRNA's translation rate.…”

Organic Wastes as Feedstocks for Non-Conventional Yeast-Based Bioprocesses

“…γ-decalactone, a fragrant compound with a peachy aroma that is used in the food industry as a flavoring agent, could be obtained by bioconversion of hydrolyzed castor oil or ricinoleic acid using wild-type strain or engineered strain of Y. lipolytica either in submerged fermentation (SmF) or solid-state fermentation (SSF). Depending on the system considered, γ-decalactone production ranged from 400 mg/L to more than 10 g/L [37,38,39,40].…”

Engineering biological systems using automated biofoundries

“…The Cello algorithm simplifies the construction of genetic circuits by borrowing from principles of design of semiconductor-electronics, and outputs a DNA sequence that codes for the circuit (Nielsen et al, 2016). DNA design algorithms have been reviewed comprehensively in these review articles (Garcia-Ruiz et al, 2016; Medema et al, 2012). …”