Pathway design using de novo steps through uncharted biochemical spaces

Akhil Kumar, Lin Wang, Chiam Yu Ng, Costas D. Maranas

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Existing retrosynthesis tools generally traverse production routes from a source to a sink metabolite using known enzymes or de novo steps. Generally, important considerations such as blending known transformations with putative steps, complexity of pathway topology, mass conservation, cofactor balance, thermodynamic feasibility, microbial chassis selection, and cost are largely dealt with in a posteriori fashion. The computational procedure we present here designs bioconversion routes while simultaneously considering any combination of the aforementioned design criteria. First, we track and codify as rules all reaction centers using a prime factorization-based encoding technique (rePrime). Reaction rules and known biotransformations are then simultaneously used by the pathway design algorithm (novoStoic) to trace both metabolites and molecular moieties through balanced bio-conversion strategies. We demonstrate the use of novoStoic in bypassing steps in existing pathways through putative transformations, assembling complex pathways blending both known and putative steps toward pharmaceuticals, and postulating ways to biodegrade xenobiotics.

Original languageEnglish (US)
Article number184
JournalNature communications
Issue number1
StatePublished - Dec 1 2018

All Science Journal Classification (ASJC) codes

  • General
  • Physics and Astronomy(all)
  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)


Dive into the research topics of 'Pathway design using de novo steps through uncharted biochemical spaces'. Together they form a unique fingerprint.

Cite this